lyngbya toxins

Summary

Summary: Toxins isolated from any species of the seaweed Lyngbya or similar chemicals from other sources, including mollusks and micro-organisms. These have been found to be potent tumor promoters. They are biosynthesized from TRYPTOPHAN; VALINE; and METHIONINE nonribosomally (PEPTIDE BIOSYNTHESIS, NUCLEIC ACID-INDEPENDENT).

Top Publications

  1. ncbi Continuing studies on the cyanobacterium Lyngbya sp.: isolation and structure determination of 15-norlyngbyapeptin A and lyngbyabellin D
    Philip G Williams
    Department of Chemistry, University of Hawaii at Manoa, Honolulu 96822, USA
    J Nat Prod 66:595-8. 2003
  2. ncbi Involvement of down-regulation-resistant protein kinase C in teleocidin inhibition of cell proliferation and calcium mobilization induced by epidermal growth factor and vasopressin in human hepatoma cells
    Y Kaneko
    First Department of Medicine, University of Tokyo, Faculty of Medicine, Japan
    Cancer Lett 71:103-8. 1993
  3. ncbi The structure of Palau'amide, a potent cytotoxin from a species of the marine cyanobacterium Lyngbya
    Philip G Williams
    Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA
    J Nat Prod 66:1545-9. 2003
  4. ncbi Apratoxin E, a cytotoxic peptolide from a guamanian collection of the marine cyanobacterium Lyngbya bouillonii
    Susan Matthew
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    J Nat Prod 71:1113-6. 2008
  5. pmc Evidence for paralytic shellfish poisons in the freshwater cyanobacterium Lyngbya wollei (Farlow ex Gomont) comb. nov
    W W Carmichael
    Department of Biological Sciences, Wright State University, Dayton, Ohio 45435, USA
    Appl Environ Microbiol 63:3104-10. 1997
  6. ncbi Aurilides B and C, cancer cell toxins from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula
    Bingnan Han
    College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA
    J Nat Prod 69:572-5. 2006
  7. ncbi Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase
    Daniel J Edwards
    College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA
    J Am Chem Soc 126:11432-3. 2004
  8. ncbi Apratoxin D, a potent cytotoxic cyclodepsipeptide from papua new guinea collections of the marine cyanobacteria Lyngbya majuscula and Lyngbya sordida
    Marcelino Gutierrez
    Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California 92093, USA
    J Nat Prod 71:1099-103. 2008
  9. ncbi New saxitoxin analogues from the freshwater filamentous cyanobacterium Lyngbya wollei
    H Onodera
    Department of Applied Biological Chemistry, Faculty of Agriculture, Tohoku University, Sendai, Japan
    Nat Toxins 5:146-51. 1997
  10. ncbi Bisebromoamide, a potent cytotoxic peptide from the marine cyanobacterium Lyngbya sp.: isolation, stereostructure, and biological activity
    Toshiaki Teruya
    Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3 14 1, Kohoku Ku, Yokohama 223 8522, Japan
    Org Lett 11:5062-5. 2009

Scientific Experts

  • Angela Capper
  • Kendal E Harr
  • Ahmed Kamal
  • Hans Paerl
  • Yu Nakagawa
  • Jillu S Yadav
  • Kimberly A Werner
  • Li Liu
  • Nicholas J Osborne
  • Emiko Ito
  • John P Berry
  • T Yasumoto
  • Y Endo
  • H Fukasawa
  • D Ma
  • Koichi Nakae
  • William H Gerwick
  • Ryo C Yanagita
  • Kazuhiro Irie
  • Toshiaki Teruya
  • Daniel J Edwards
  • Hiroaki Kamachi
  • Hendrik Luesch
  • Philip G Williams
  • Sarah E Ongley
  • Christopher C Thornburg
  • Adam C Jones
  • Keisuke Tanaka
  • Akira Murakami
  • Harukuni Tokuda
  • Tatsuro Kawamura
  • George E Chlipala
  • Minh U Huynh
  • Marcy J Balunas
  • Hiroyuki Kikuchi
  • Kiyotake Suenaga
  • Richard E Moore
  • Valerie J Paul
  • Hiroaki Sasaki
  • Wesley Y Yoshida
  • Susan Matthew
  • Marcelino Gutierrez
  • Teatulohi Matainaho
  • Benjamin R Clark
  • Niclas Engene
  • H Fujiki
  • Marian E van Apeldoorn
  • Jay A Read
  • Tianying An
  • S Wang
  • Paulo Vital
  • Bingnan Han
  • K Shudo
  • David Tanner
  • Janne E Tønder
  • L Levine
  • W I Li
  • S Okabe
  • A P Kozikowski
  • Y Kaneko
  • Ivanka Teneva
  • T Okino
  • W H Gerwick
  • Brian D Dangel
  • Brian L Marquez
  • Henner Knust
  • Xiaoying Bian
  • Rolf Muller
  • Youming Zhang
  • Kazuma Murakami
  • Justyna Sikorska
  • Brett A Neilan
  • Kerry L McPhail
  • Rocky Chau
  • Lamiaa A Shaala
  • Nobutaka Suzuki
  • Elise S Cowley
  • Diaa T A Youssef
  • Jane E Ishmael
  • Sabine Ottilie
  • Alessandra S Eustáquio
  • L M Nogle
  • Lena Gerwick
  • Bradley S Moore
  • Hitomi Otaka
  • Kazutoshi Shindo
  • M Suganuma
  • W W Carmichael
  • Etsu Tashiro
  • Kohei Matsubara

Detail Information

Publications111 found, 100 shown here

  1. ncbi Continuing studies on the cyanobacterium Lyngbya sp.: isolation and structure determination of 15-norlyngbyapeptin A and lyngbyabellin D
    Philip G Williams
    Department of Chemistry, University of Hawaii at Manoa, Honolulu 96822, USA
    J Nat Prod 66:595-8. 2003
    ..Lyngbyabellin D (3) displayed an IC(50) value of 0.1 microM against the KB cell line...
  2. ncbi Involvement of down-regulation-resistant protein kinase C in teleocidin inhibition of cell proliferation and calcium mobilization induced by epidermal growth factor and vasopressin in human hepatoma cells
    Y Kaneko
    First Department of Medicine, University of Tokyo, Faculty of Medicine, Japan
    Cancer Lett 71:103-8. 1993
    ..This down-regulation-resistant PKC is suggested to be responsible for the inhibitory effect of teleocidin on cell proliferation and calcium mobilization induced by epidermal growth factor and vasopressin...
  3. ncbi The structure of Palau'amide, a potent cytotoxin from a species of the marine cyanobacterium Lyngbya
    Philip G Williams
    Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA
    J Nat Prod 66:1545-9. 2003
    ..The assignment of S rather than R stereochemistry at C-37 is discussed in detail...
  4. ncbi Apratoxin E, a cytotoxic peptolide from a guamanian collection of the marine cyanobacterium Lyngbya bouillonii
    Susan Matthew
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    J Nat Prod 71:1113-6. 2008
    ..The 5- to 15-fold reduced activity compared with apratoxin A (2) is attributed to the dehydration in the long-chain polyketide unit, which could affect the conformation of the molecule...
  5. pmc Evidence for paralytic shellfish poisons in the freshwater cyanobacterium Lyngbya wollei (Farlow ex Gomont) comb. nov
    W W Carmichael
    Department of Biological Sciences, Wright State University, Dayton, Ohio 45435, USA
    Appl Environ Microbiol 63:3104-10. 1997
    ..Fifty field samples were placed in unialgal culture and grown under defined culture conditions. Toxicity and signs of poisoning for these laboratory-grown strains of L. wollei were similar to those of the field collection samples...
  6. ncbi Aurilides B and C, cancer cell toxins from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula
    Bingnan Han
    College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA
    J Nat Prod 69:572-5. 2006
    ....
  7. ncbi Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase
    Daniel J Edwards
    College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA
    J Am Chem Soc 126:11432-3. 2004
    ..LtxC was heterologously produced and purified from E. coli and shown to catalyze the transfer of a geranyl group to (-)-indolactam V as the final step in the biosynthesis of lyngbyatoxin A...
  8. ncbi Apratoxin D, a potent cytotoxic cyclodepsipeptide from papua new guinea collections of the marine cyanobacteria Lyngbya majuscula and Lyngbya sordida
    Marcelino Gutierrez
    Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California 92093, USA
    J Nat Prod 71:1099-103. 2008
    ..Apratoxin D (1) showed potent in vitro cytotoxicity against H-460 human lung cancer cells with an IC 50 value of 2.6 nM...
  9. ncbi New saxitoxin analogues from the freshwater filamentous cyanobacterium Lyngbya wollei
    H Onodera
    Department of Applied Biological Chemistry, Faculty of Agriculture, Tohoku University, Sendai, Japan
    Nat Toxins 5:146-51. 1997
    ..The presence of acetate in the side chain resulted in a sevenfold to 17-fold times decrease in mouse toxicity compared to their carbamoyl counterparts, while the reduction at C-12 resulted in a complete loss of mouse toxicity...
  10. ncbi Bisebromoamide, a potent cytotoxic peptide from the marine cyanobacterium Lyngbya sp.: isolation, stereostructure, and biological activity
    Toshiaki Teruya
    Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3 14 1, Kohoku Ku, Yokohama 223 8522, Japan
    Org Lett 11:5062-5. 2009
    ..Bisebromoamide (1) exhibited potent protein kinase inhibition: the phosphorylation of ERK in NRK cells by PDGF-stimulation was selectively inhibited by treatment with 10-0.1 microM of 1...
  11. ncbi The toxins of Lyngbya majuscula and their human and ecological health effects
    N J Osborne
    National Research Centre for Environmental Toxicology, Brisbane, Queensland, Australia
    Environ Int 27:381-92. 2001
    ..The potential exists for toxins from Lyngbya majuscula affecting ecological health and in particular marine reptiles...
  12. pmc Structures of pahayokolides A and B, cyclic peptides from a Lyngbya sp
    Tianying An
    Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, USA
    J Nat Prod 70:730-5. 2007
    ..These peptides were purified from a new species of cyanobacteria of the genus Lyngbya, which was isolated from a periphyton mat from the Florida Everglades...
  13. pmc Dragonamide E, a modified linear lipopeptide from Lyngbya majuscula with antileishmanial activity
    Marcy J Balunas
    Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, USA
    J Nat Prod 73:60-6. 2010
    ..Biosynthetic differences among marine compounds with a terminal free amide are also discussed...
  14. ncbi Health effects of recreational exposure to Moreton Bay, Australia waters during a Lyngbya majuscula bloom
    N J Osborne
    School of Population Health, University of Queensland, Brisbane, Queensland, Australia
    Environ Int 33:309-14. 2007
    ..In conclusion, high numbers of participants reported symptoms after exposure to waters subject to L. majuscula blooms but only a small number appeared to be serious in nature suggesting limited exposure to toxins...
  15. ncbi The freshwater cyanobacterium Lyngbya aerugineo-coerulea produces compounds toxic to mice and to mammalian and fish cells
    Ivanka Teneva
    Junior Research Group, Molecular Animal Cell Toxicology, UFZ Centre for Environmental Research, Permoserstrasse 15, 04318 Leipzig, Germany
    Environ Toxicol 18:9-20. 2003
    ....
  16. ncbi The fate of Lyngbya majuscula toxins in three potential consumers
    Angela Capper
    Smithsonian Marine Station, Fort Pierce, FL 34949, USA
    J Chem Ecol 31:1595-606. 2005
    ..The high levels of secondary metabolites observed in both the anaspidean and the cephalapsidean species suggest that these toxins may bioaccumulate through marine food chains...
  17. ncbi Lyngbyaloside B, a new glycoside macrolide from a Palauan marine cyanobacterium, Lyngbya sp
    Hendrik Luesch
    Department of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USA
    J Nat Prod 65:1945-8. 2002
    ..The relative stereochemistry for the 12 stereocenters is proposed on the basis of proton-proton spin-coupling constants and ROESY data...
  18. ncbi C-C bond formation via C-H bond activation: synthesis of the core of teleocidin B4
    Brian D Dangel
    Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027, USA
    J Am Chem Soc 124:11856-7. 2002
    ..Noteworthy is the fact that steps 1 and 3 critically depended on the directing role of the aniline nitrogen (directed C-H bond functionalization)...
  19. ncbi Apoptosis and nuclear levels of p53 protein and proliferating cell nuclear antigen in human hepatoma cells cultured with tumor promoters
    Y Kaneko
    First Department of Medicine, University of Tokyo, Japan
    Cancer Lett 91:11-7. 1995
    ..Both tumor promoters suppressed the increase in nuclear p53 protein, suggesting that an inadequate DNA repair due to the reduced nuclear accumulation of p53 protein might be playing important role in enhancing carcinogenesis...
  20. ncbi Resistance of human bronchial epithelial cells to teleocidin in a two-stage carcinogenesis experiment
    S Teshima
    Pathology Division, National Cancer Center Research Institute, Tokyo, Japan
    Acta Pathol Jpn 37:1859-65. 1987
    ..Thus, teleocidin had an effect on mouse tissues, but seemed to have no effect on human bronchial cells, although it is uncertain whether the grafted human bronchi were initiated by DMBA...
  21. pmc Dermatitis associated with exposure to a marine cyanobacterium during recreational water exposure
    Nicholas J Osborne
    Gut and Liver, Murdoch Childrens Research Institute, Flemington Road, Melbourne, Australia
    BMC Dermatol 8:5. 2008
    ..majuscula. This coincided with the presence of a bloom of L. majuscula...
  22. ncbi Enhancing effect of tumor promoters, phorbol esters and teleocidins on nuclear receptor-mediated transcription
    H Fukasawa
    Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan
    Biol Pharm Bull 23:1414-7. 2000
    ..These results suggest this reporter system is useful for the evaluation of effects on the gene expression of various tumor promoters, including non-TPA type...
  23. ncbi Phosphorylations of Mr 34,000 and 40,000 proteins by protein kinase C in mouse epidermis in vivo
    K Chida
    Department of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Japan
    Cancer Res 48:4018-23. 1988
    ..Furthermore, p34 and p40 were phosphorylated by purified PKC in a cell-free system. These results indicate that p34 and p40 are phosphorylated by PKC in mouse epidermis in vivo and may be involved in tumor promotion...
  24. ncbi Inhibitory effects of 12-O-tetradecanoylphorbol-13-acetate and teleocidin B induced Epstein-Barr virus by saponin and its related compounds
    H Tokuda
    Department of Microbiology, Faculty of Medicine, Kyoto University, Japan
    Cancer Lett 40:309-17. 1988
    ....
  25. ncbi Novobiocin modulates cytokeratin assembly and differentiation of human hepatoma cells induced by butyrate and teleocidin
    A Tsukamoto
    First Department of Medicine, University of Tokyo, Faculty of Medicine, Japan
    Cancer Lett 60:51-7. 1991
    ..These results suggest that butyrate and teleocidin induce cell differentiation via distinct signaling pathway and that novobiocin and butyrate can be used as subsidiary drugs in preventing the growth of hepatoma...
  26. ncbi Generation of 'Unnatural Natural Product' library and identification of a small molecule inhibitor of XIAP
    Tatsuro Kawamura
    Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3 14 1 Hiyoshi, Kohoku Ku, Yokohama 223 8522, Japan
    Bioorg Med Chem 19:4377-85. 2011
    ..Furthermore, C38OX6 sensitized cancer cells to anticancer drugs, whereas the unconverted natural product did not. These findings suggest that our library could be a useful source for drug seeds...
  27. ncbi Suppression by protein kinase C inhibitors of tumor promoter enhancement of Epstein-Barr virus-induced growth transformation
    T Kinoshita
    Department of Virology, Hokkaido University School of Medicine, Sapporo, Japan
    Anticancer Res 10:1051-4. 1990
    ..All these events were suppressed by exposure to 10-100 nM UCN-01 or to calphostin C. Our findings suggest that the tumor promoter enhancement of EBV growth transformation is probably mediated by PKC...
  28. ncbi The effects of teleocidin and aplysiatoxin tumor promoters on epithelial tight junctions and transepithelial permeability: comparison to phorbol esters
    J M Mullin
    Lankenau Medical Research Center, Philadelphia, PA
    Carcinogenesis 11:377-85. 1990
    ..These four tumor promoters, TPA, PDBU, teleocidin and aplysiatoxin, are all known protein kinase C activators, and support the case for protein-kinase-C-mediated control of tight junctional permeability...
  29. pmc Cross-resistance to tumour promoters in human cancer cell lines resistant to adriamycin or cisplatin
    K Nishio
    Pharmacology Division, National Cancer Centre Research Institute, Tokyo, Japan
    Br J Cancer 62:415-9. 1990
    ..These results suggest the presence of another common mechanism for resistance to ADM and CDDP as well as to TPA- or non-TPA-type tumour promoters...
  30. ncbi Structure-activity studies on the side chain of a simplified analog of aplysiatoxin (aplog-1) with anti-proliferative activity
    Hiroaki Kamachi
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    Bioorg Med Chem 21:2695-702. 2013
    ..These results would facilitate rapid preparation of molecular probes to examine the mechanism of the unique biological activities of aplog-1...
  31. ncbi Effects of aplysiatoxin and debromoaplysiatoxin on growth and differentiation of normal human bronchial epithelial cells
    J C Willey
    Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20205
    Cell Biol Toxicol 1:145-54. 1984
    ....
  32. ncbi A case study in conformation design: learning by doing
    Henner Knust
    Fachbereich Chemie der Philipps Universität Marburg, D 35032 Marburg, Germany
    Chem Rec 2:405-18. 2002
    ....
  33. ncbi The first total synthesis of nhatrangin A
    Ahmed Kamal
    Medicinal Chemistry and Pharmacology, CSIR Indian Institute of Chemical Technology, Hyderabad, 500007, India
    Org Biomol Chem 11:4442-8. 2013
    ..The first total synthesis of nhatrangin A has been achieved. Pivotal bond forming events in the synthesis include Brown crotylboration, olefin cross-metathesis, Sharpless asymmetric dihydroxylation and Yamaguchi esterification...
  34. ncbi Total synthesis of nhatrangin A
    Jhillu Singh Yadav
    Division of Natural Products Chemistry, CSIR Indian Institute of Chemical Technology, Hyderabad 500007, India
    J Org Chem 78:8524-30. 2013
    ..Synthesis of nhatrangin A was accomplished by coupling of dihydroxy acid 12 with β-hydroxyallyl ester (obtained from 11) under Yamaguchi reaction conditions followed by a one-pot deprotection of all protecting groups. ..
  35. pmc High-titer heterologous production in E. coli of lyngbyatoxin, a protein kinase C activator from an uncultured marine cyanobacterium
    Sarah E Ongley
    School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney 2052, Australia
    ACS Chem Biol 8:1888-93. 2013
    ..The successful production of the nonribosomal peptide lyngbyatoxin A in E. coli also opens the possibility for future heterologous expression, characterization, and exploitation of other cyanobacterial natural product pathways. ..
  36. ncbi Comparison of the partition coefficient and skin penetration of a marine algal toxin (lyngbyatoxin A)
    R G Stafford
    Department of Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Alabama
    Food Chem Toxicol 30:795-801. 1992
    ..2 (respectively) after 1 hr of topical exposure. The amount of lyngbyatoxin A in the dermis and receptor fluid did not change significantly over time...
  37. ncbi Absence of synergistic effects on tumor promotion in CD-1 mouse skin by simultaneous applications of two different types of tumor promoters, okadaic acid and teleocidin
    M Suganuma
    Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan
    Cancer Res 53:1012-6. 1993
    ..The effect of cotreatment of okadaic acid and teleocidin is discussed at the molecular level...
  38. ncbi Comparison of 12-O-tetradecanoylphorbol-13-acetate and teleocidin for induction of epidermal hyperplasia, activation of epidermal PKC isozymes and skin tumor promotion in SENCAR and C57BL/6 mice
    A Imamoto
    Department of Carcinogenesis, University of Texas M D Anderson Cancer Center, Smithville 78957
    Carcinogenesis 14:719-24. 1993
    ..Taken together, the current data suggest that factors in addition to the induction of sustained epidermal hyperplasia, control responsiveness of C57BL/6 mice to skin tumor promotion by diverse promoting stimuli...
  39. pmc Natural products chemistry and taxonomy of the marine cyanobacterium Blennothrix cantharidosmum
    Benjamin R Clark
    Scripps Institution of Oceanography, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093 0212, USA
    J Nat Prod 71:1530-7. 2008
    ..Nevertheless, these are the first natural products to be reported from this genus, and this inspired a detailed morphologic and 16S rDNA-based phylogenetic analysis of the producing organism...
  40. ncbi Studies of the formation of all-carbon quaternary centres, en route to lyngbyatoxin A. A comparison of phenyl and 7-substituted indole systems
    Janne E Tønder
    Department of Chemistry, Technical University of Denmark, Building 201, Kemitorvet, DK 2800 Kgs Lyngby, Denmark
    Org Biomol Chem 2:1447-55. 2004
    ..In related studies, copper catalysed conjugate addition of EtMgBr to the tricyclic lactam 6-methyl-pyrrolo[3,2,1-ij]quinolin-4-one gave a maximum of 20% of the 1,4-addition product...
  41. ncbi Role of the phenolic hydroxyl group in the biological activities of simplified analogue of aplysiatoxin with antiproliferative activity
    Ryo C Yanagita
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan
    Bioorg Med Chem Lett 20:6064-6. 2010
    ..Moreover, PKC isozyme selectivity of 3 was similar to that of 1, suggesting non-PKC receptors for these compounds to play some roles in the anti-tumor-promoting activity of 1...
  42. ncbi Modification of cellular membrane functions by pendolmycin
    K Umezawa
    Institute of Microbial Chemistry, Tokyo
    Jpn J Cancer Res 80:15-8. 1989
    ..Thus, pendolmycin was as potent as teleocidin B and phorbol ester tumor promoters in modification of cell membrane functions, while having the simplest structure among them...
  43. pmc Modulation of phospholipase A2 activity by the tumour promoters phorbol esters and teleocidin
    K Y Nam
    Department of Polymer Chemistry, Kyoto University, Japan
    Biochem J 268:169-73. 1990
    ..However, the effects of tumour promoters on PLA2 activity was not related to their potencies as inflammatory and tumour-promoting agents...
  44. pmc Structural basis of protein kinase C activation by tumor promoters
    H Nakamura
    Department of Chemistry, Harvard University, Cambridge, MA 02138
    Proc Natl Acad Sci U S A 86:9672-6. 1989
    ..Experimentally testable predictions are made concerning the interactions with PKC of several classes of tumor PKC activators...
  45. pmc The pharmacophore of debromoaplysiatoxin responsible for protein kinase C activation
    F H Kong
    Department of Chemistry, Harvard University, Cambridge, MA 02138
    Proc Natl Acad Sci U S A 88:1973-6. 1991
    ..These findings provide strong experimental support for our structural model of protein kinase C activation...
  46. ncbi Enzymatic production of (-)-indolactam V by LtxB, a cytochrome P450 monooxygenase
    Minh U Huynh
    Department of Chemistry and Biochemistry, California State University, Chico, 400 W 1st Street, Chico, California 95929, USA
    J Nat Prod 73:71-4. 2010
    ..The relaxed substrate specificity of LtxB, along with the relaxed specificity of the prenyltransferase, LtxC, allowed for the enzymatic production of a series of (-)-indolactam V and lyngbyatoxin analogues...
  47. pmc Okadaic acid: an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter
    M Suganuma
    Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan
    Proc Natl Acad Sci U S A 85:1768-71. 1988
    ..2 microM. Therefore, the actions of okadaic acid and phorbol ester may be mediated in different ways. These results show that okadaic acid is a non-TPA-type tumor promoter in mouse skin carcinogenesis...
  48. ncbi Structural investigation of protein kinase C inhibitors
    D Barak
    Department of Biophysical Science, Roswell Park Memorial Institute, Buffalo, NY 14263, USA
    J Mol Struct 230:419-29. 1991
    ..The model shows two sites of hydrophobic interaction and enables the inhibitory activity of gossypol to be accounted for...
  49. pmc A receptor model for tumor promoters: rational superposition of teleocidins and phorbol esters
    A Itai
    Faculty of Pharmaceutical Sciences, University of Tokyo, Japan
    Proc Natl Acad Sci U S A 85:3688-92. 1988
    ..Their mutual spatial arrangements are most important for biological activity...
  50. ncbi A new teleocidin analog from Streptomyces sp. MM216-87F4 induces substance P release from rat dorsal root ganglion neurons
    Koichi Nakae
    Microbial Chemistry Research Center, 3 14 23 Kamiosaki, Shinagawa ku, Tokyo 141 0021, Japan
    J Antibiot (Tokyo) 59:11-7. 2006
    ..This study provides the first observation that a teleocidin analog without a free hydroxyl group at C-14 acts as a PKC activator and directly induces the release of excitatory neuropeptide...
  51. pmc Nhatrangins A and B, aplysiatoxin-related metabolites from the marine cyanobacterium Lyngbya majuscula from Vietnam
    George E Chlipala
    Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 S Wood Street, Chicago, Illinois 60612, USA
    J Nat Prod 73:784-7. 2010
    ..3 mg of compound. LC-MS analysis was utilized to direct the isolation of additional material as well as the isolation of 2. Conformational analysis was completed using J-based coupling constant analysis and selective NOE experiments...
  52. ncbi Co-ordinate expression of c-fos, p53 and cytokeratin genes during the alteration of growth of human hepatoma cells. mRNA levels measured by reverse transcription and polymerase chain reaction
    Y Kaneko
    First Department of Medicine, University of Tokyo, Faculty of Medicine, Japan
    Cancer Lett 66:155-64. 1992
    ..Sequential alterations of the expression of c-fos, p53, c-myc and cytokeratin genes induced by teleocidin may be responsible for the morphological and functional changes of hepatoma cells induced by this tumor promoter...
  53. ncbi Evaluation of Streptomyces coelicolor A3(2) as a heterologous expression host for the cyanobacterial protein kinase C activator lyngbyatoxin A
    Adam C Jones
    Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093 0212, USA
    FEBS J 279:1243-51. 2012
    ..Successful expression of lyngbyatoxin A proteins in Streptomyces provides a new platform for biochemical investigation of natural product enzymes from Moorea strains...
  54. pmc Apratoxin H and apratoxin A sulfoxide from the Red Sea cyanobacterium Moorea producens
    Christopher C Thornburg
    Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, United States
    J Nat Prod 76:1781-8. 2013
    ....
  55. ncbi Acquisition of a growth-inhibitory response to phorbol ester involves DNA damage
    Y Sun
    Biological Carcinogenesis and Development Program, National Cancer Institute Frederick Cancer Research and Development Center, Maryland 21702
    Cancer Res 52:1907-15. 1992
    ..Conventional subcultivation may have selected for the former subpopulation. The sensitive subpopulation may have been irreversibly inhibited as a result of TPA-induced cell killing, possibly apoptosis...
  56. ncbi Debromoaplysiatoxin in Lyngbya-dominated mats on manatees (Trichechus manatus latirostris) in the Florida King's Bay ecosystem
    Kendal E Harr
    FVP Consultants, Inc, 7805 SW 19th Place, Gainesville, FL 32607, USA
    Toxicon 52:385-8. 2008
    ..DAT was also detected (up to 1.19 microg/g WWLAE) in Lyngbya-dominated mats collected from manatee dorsa. Ulcerative dermatitis found on manatees is associated with, but has not been proven to be caused by DAT...
  57. ncbi Sarcophytols A and B inhibit tumor promotion by teleocidin in two-stage carcinogenesis in mouse skin
    H Fujiki
    Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan
    J Cancer Res Clin Oncol 115:25-8. 1989
    ..The effective concentrations of sarcophytols A and B were in the microgram range with an equimolar amount of teleocidin...
  58. ncbi Localization of granular components in ADP- and/or teleocidin-stimulated human blood platelets as revealed by immunocytochemical methods
    H Kawakami
    Department of Anatomy, Kyorin University School of Medicine, Tokyo, Japan
    Acta Haematol 82:75-80. 1989
    ..When both teleocidin and ADP were administered, both alpha-granular and dense-granular components moved into the swollen OCS...
  59. ncbi The lyngbyatoxin biosynthetic assembly line: chain release by four-electron reduction of a dipeptidyl thioester to the corresponding alcohol
    Jay A Read
    Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, 240 Longwood Avenue Boston, Massachusetts 02115, USA
    J Am Chem Soc 129:15762-3. 2007
    ..By employing a ketone mimic of the aldehyde intermediate, as well as a specifically deuterated NADPH, it was further demonstrated that the pro-S hydride of the cofactor is transferred to the re face of the carbonyl group...
  60. ncbi Effects of phorbol ester and teleocidin on Ca2+-induced fusion of liposomes
    K Nam
    Department of Polymer Chemistry, Kyoto University, Japan
    Biochem Biophys Res Commun 165:1256-61. 1989
    ..Thus, Ca2+-induced fusion of PS vesicles was shown to be sensitive to defects of the membrane surface, but insensitive to defects of the hydrophobic core of the lipid membrane...
  61. ncbi Toxins of cyanobacteria
    Marian E van Apeldoorn
    Centre for Substances and Integrated Risk Assessment, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
    Mol Nutr Food Res 51:7-60. 2007
    ..Official regulations for other cyanotoxins have not been established, although some (provisional) guideline values have been derived for microcystins in drinking water by WHO and several countries...
  62. ncbi The conformations and electrostatic potential maps of phorbol esters, teleocidins and ingenols
    C Thomson
    Chemistry Department, University of St Andrews, Fife, UK
    Carcinogenesis 10:531-40. 1989
    ..Electrostatic potentials were calculated and displayed using an in-house program 3D2, while superpositions of molecules were carried out using CHEM-X...
  63. ncbi Efficient and highly enantioselective formation of the all-carbon quaternary stereocentre of lyngbyatoxin A
    Paulo Vital
    Department of Chemistry, Technical University of Denmark, Building 201, Kemitorvet, DK 2800, Kgs Lyngby, Denmark
    Org Biomol Chem 4:4292-8. 2006
    ....
  64. ncbi Comparison of the histological changes in the skin of DBA/2 and C57BL/6 mice following exposure to various promoting agents
    M Naito
    University of Texas System Cancer Center, Smithville 78957
    Carcinogenesis 8:1807-15. 1987
    ..abstract truncated at 400 words)..
  65. ncbi A radioimmunoassay for the teleocidins using 26 (2'-aminoethylthio)-tetrahydroteleocidin A-2 as hapten
    L Levine
    Department of Biochemistry, Brandeis University, Waltham, MA 02254
    Carcinogenesis 9:1629-33. 1988
    ..3 pmol) greater than (-)-indolactam-V (3.7 nmol) greater than teleocidin B-4 (13 nmol). Maitotoxin, aplysiatoxin, palytoxin, mezerein, okadaic acid and 12-O-tetradecanoylphorbol-13-acetate did not inhibit at the levels tested...
  66. ncbi Protein kinase C activators of the teleocidin family decrease the IgE-binding capacity of rat basophilic leukemia cells
    C Gaveriaux
    Preclinical Research Department, Sandoz, Basel, Switzerland
    Int Arch Allergy Appl Immunol 86:465-71. 1988
    ..It is suggested that the down-regulation of IgE receptor expression by these tumor promoters is mediated through protein kinase C activation and phosphorylation of the Fc epsilon R...
  67. pmc Pharmacology and toxicology of pahayokolide A, a bioactive metabolite from a freshwater species of Lyngbya isolated from the Florida Everglades
    John P Berry
    Marine Biology and Fisheries, Rosenstiel School of Marine and Atmospheric Science, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33149, USA
    Comp Biochem Physiol C Toxicol Pharmacol 139:231-8. 2004
    ....
  68. ncbi Identification of tumor promoters by their inhibitory effect on intercellular transfer of lucifer yellow
    I V Budunova
    Laboratory of Carcinogen Screening Methods, All Union Cancer Research Center of the AMS USSR, Moscow
    Cell Biol Toxicol 5:77-89. 1989
    ..All the promoters investigated had a reversible effect on the dye transfer. The value of the dye transfer method for promoter screening is discussed...
  69. ncbi The effects of tumor promoters on HTLV-1 expression in a low-virus producer and a non-virus producer cell line
    L J Carter
    Biotechnology Center, Ohio State University, Columbus 43210
    Cancer Lett 39:329-38. 1988
    ..Chemicals did not induce HTLV-I antigen expression in the C63/CI(II-2) cell line. No enhancement of reverse transcriptase activity or alteration of proviral organization was observed after chemical treatment of MT-1 cells...
  70. ncbi Structural requirements of lyngbyatoxin A for activation and downregulation of protein kinase C
    A Basu
    Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261
    Biochemistry 31:3824-30. 1992
    ..Constitutive expression of PKC beta and PKC gamma isoforms was low in HeLa cells and was not affected significantly by TPA or lyngbyatoxin A analogues.(ABSTRACT TRUNCATED AT 250 WORDS)..
  71. ncbi Active conformation of a tumor promoter, teleocidin. A molecular dynamics study
    T Kawai
    Faculty of Pharmaceutical Sciences, University of Tokyo
    J Med Chem 35:2248-53. 1992
    ..The high-temperature MD method proved to be very useful for predicting the preferred structures of these cyclic compounds, in which the overall stabilities are strongly influenced by the conformations of substituent groups on the ring...
  72. ncbi Effect of tumour promoters and non-genotoxic carcinogens on terminal differentiation and proliferation in mouse teratoma XB2 cells cultured in low calcium medium
    S D Hewitt
    Cancer Research Unit, University of York, Heslington, UK
    Carcinogenesis 11:371-5. 1990
    ..We suggest that this culture system may provide a useful model for studies of the mechanism of promotion and non-genotoxic carcinogenesis in epithelial tissues...
  73. ncbi Vacuole formation and cytokeratin rearrangement of hepatoma cells induced by teleocidin are not associated with down-regulation of protein kinase C
    Y Kaneko
    First Department of Medicine, University of Tokyo, Faculty of Medicine, Japan
    Cancer Res 51:2677-82. 1991
    ..From these results it can be speculated that the morphological transformation and reduced cell proliferation induced by teleocidin may be mediated by still unknown mechanisms unrelated to protein kinase C...
  74. pmc Biosynthetic origin of the 3-amino-2,5,7,8-tetrahydroxy-10-methylundecanoic acid moiety and absolute configuration of pahayokolides A and B
    Li Liu
    Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, USA
    J Nat Prod 74:1535-8. 2011
    ..Incorporation of labeled leucine and acetate precursors into the pahayokolides has established that Athmu is derived from a leucine or α-keto isocaproic acid starter unit, which is further extended with three acetate units...
  75. ncbi Enhanced induction of epidermal ornithine decarboxylase activity in C57BL/6 compared to DBA/2 mice by protein kinase C-activating skin tumor promoters: relevance to genetically mediated differences in promotion susceptibility
    A Imamoto
    Department of Carcinogenesis, University of Texas M D Anderson Cancer Center, Smithville 78957
    Carcinogenesis 13:177-82. 1992
    ....
  76. ncbi Modulation of synovial fibroblast plasminogen activator and plasminogen activator inhibitor production by protein kinase C
    J Uhl
    Department of Inflammation, Sterling Research Group, Rennselaer, NY 12144
    Biochim Biophys Acta 1097:283-8. 1991
    ..These results suggest that activation of PKC may play an important role in regulating increased PA production associated with joint destruction in rheumatoid arthritis (RA)...
  77. ncbi Synthesis of structural analogues of lyngbyatoxin A and their evaluation as activators of protein kinase C
    A P Kozikowski
    Neurochemistry Research, Mayo Clinic Jacksonville, Florida 32224
    J Med Chem 34:2420-30. 1991
    ..Introduction of a hydroxyl group on the C-7 appendage was found to dramatically decrease compound 3's ability to activate PKC. This result is interpreted in terms of the decreased ability of 3 to associate with the membrane bilayer...
  78. ncbi Differential activation and inhibition of lymphocyte proliferation by phorbol esters, mezerein, teleocidin, and okadaic acid
    D S Grove
    Department of Molecular and Cell Biology, Pennsylvania State University, University Park 16802
    Cancer Res 51:82-8. 1991
    ..In no case was the modulation of protein kinase C separated from the effects on IL-2 production and proliferation...
  79. ncbi The stereochemical requirement for protein kinase C activation by 3-methyldiglycerides matches that found in naturally occurring tumor promoters aplysiatoxins
    F Kong
    Department of Chemistry, Harvard University, Cambridge, MA 02138
    FEBS Lett 274:203-6. 1990
    ..This finding strengthens the view that the structurally diverse tumor promotors contain the embedded diglyceride-like pharmacophore...
  80. ncbi Effects of lyngbyatoxin A from the blue-green alga Lyngbya majuscula on rabbit aorta contractions
    C P Robinson
    College of Pharmacy, University of Oklahoma, Oklahoma City 73190
    Toxicon 29:1009-17. 1991
    ..Thus, lyngbyatoxin A contracts the rabbit aorta by an extracellular and intracellular calcium-, endothelium- and neuron-independent mechanism similar to the protein kinase C activating phorbol esters...
  81. ncbi A simple analogue of tumor-promoting aplysiatoxin is an antineoplastic agent rather than a tumor promoter: development of a synthetically accessible protein kinase C activator with bryostatin-like activity
    Yu Nakagawa
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    J Am Chem Soc 131:7573-9. 2009
    ..This study provides a synthetically accessible PKC activator with bryo-1-like activities, which could be another therapeutic lead for cancer, AD, and AIDS...
  82. ncbi Rapid screening method for inhibitors of protein kinase C
    H Osada
    Antibiotics Laboratory, RIKEN, Institute of Physical and Chemical Research, Saitama, Japan
    J Antibiot (Tokyo) 41:925-31. 1988
    ..Teleocidins A and B, and tautomycin (a new antibiotic isolated in our laboratory) were identified as activators of PKC, and also staurosporine and isoflavones (daidzein and genistein) as inhibitors...
  83. pmc Analysis of the stimulative effect of thapsigargin, a non-TPA-type tumour promoter, on arachidonic acid metabolism in rat peritoneal macrophages
    K Ohuchi
    Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan
    Br J Pharmacol 94:917-23. 1988
    ..6. These results suggest that thapsigargin stimulates arachidonic acid release by a mechanism different from that of TPA, viz by acting as a selective Ca2+ mobilizer, but not by activating protein kinase C as TPA does...
  84. ncbi [From cancer prevention to cancer treatment]
    K Shudo
    Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan
    Yakugaku Zasshi 120:987-95. 2000
    ..Further retinoid research yielded retinoids antagonists, and then RXR(retinoic acid-X-receptor)-agonists and RXR-antagonists. These ligands have a big potential in the therapy of diabetes and obesity...
  85. ncbi Isolation and structure of the cytotoxin lyngbyabellin B and absolute configuration of lyngbyapeptin A from the marine cyanobacterium Lyngbya majuscula
    H Luesch
    Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA
    J Nat Prod 63:1437-9. 2000
    ..The known modified tetrapeptide lyngbyapeptin A (3) has also been found in the same extract, and its absolute stereochemistry could be determined for the first time...
  86. ncbi Modeling, chemistry, and biology of the benzolactam analogues of indolactam V (ILV). 2. Identification of the binding site of the benzolactams in the CRD2 activator-binding domain of PKCdelta and discovery of an ILV analogue of improved isozyme selectivit
    A P Kozikowski
    Institute for Cognitive and Computational Sciences and Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007 2197, USA
    J Med Chem 40:1316-26. 1997
    ..Lastly, we report inhibition of cellular proliferation of two different breast carcinoma cell lines by the benzolactam 5 and show that the compound preferentially down-regulates PKCbeta in both cell lines...
  87. ncbi Probing the binding of indolactam-V to protein kinase C through site-directed mutagenesis and computational docking simulations
    S Wang
    Drug Discovery Program, Georgetown Institute for Cognitive and Computational Sciences, Research Building, Room EP07, Georgetown University Medical Center, 3970 Reservoir Road, Washington, D C 20007, USA
    J Med Chem 42:3436-46. 1999
    ....
  88. ncbi Amplification of arachidonic acid metabolism in rat liver cells (the C-9 cell-line) by tosyl-L-phenylalanine chloromethyl ketone and phenylmethyl-sulfonyl fluoride
    L Levine
    Department of Biochemistry, Brandeis University, Waltham, MA 02254, USA
    Prostaglandins 50:89-101. 1995
    ..While phenylmethyl-sulfonyl fluoride's amplification of PGI2 production by cells treated with TPA was blocked by prior incubation with TPA for 20 h, a similar block of amplification in EGF-treated cells was not observed...
  89. ncbi Morphological observations of diarrhea in mice caused by aplysiatoxin, the causative agent of the red alga Gracilaria coronopifolia poisoning in Hawaii
    E Ito
    Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Japan
    Toxicon 36:1913-20. 1998
    ..The cecum was the main target of the diarrhea. After the diarrhea ended, the number of goblet cells was increased remarkably and many fine cracks were left on the surface of the epithelium...
  90. ncbi Proteolysis negatively regulates agonist-stimulated arachidonic acid metabolism
    L Levine
    Department of Biochemistry, Brandeis University, Waltham, MA 02254, USA
    Cell Signal 10:653-9. 1998
    ..Inhibition of proteolytic activity amplifies agonist-stimulated arachidonic acid metabolism in these cells...
  91. ncbi Twist form of teleocidin derivatives is active in in vivo tumor promotion by (-)-benzolactam-V8-310
    S Okabe
    Saitama Cancer Center Research Institute, Japan
    Biol Pharm Bull 21:465-8. 1998
    ..Also (-)-BL-V8-310 is a new synthetic tumor promoter designed from data obtained using the receptor cavity model of TPA-type tumor promoters...
  92. ncbi Clarification of the binding mode of teleocidin and benzolactams to the Cys2 domain of protein kinase Cdelta by synthesis of hydrophobically modified, teleocidin-mimicking benzolactams and computational docking simulation
    Y Endo
    Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1, Hongo, Bunkyo ku, Tokyo 113, Japan
    J Med Chem 41:1476-96. 1998
    ..The model explains well the remarkable difference in activity between 5 and its analogue having a bulky substituent at C-8...
  93. ncbi Anticarcinogenic activity of green tea polyphenols
    A Komori
    Cancer Prevention Division, National Cancer Center Research Institute, Tokyo
    Jpn J Clin Oncol 23:186-90. 1993
    ..The sealing effect would account for reversible growth arrest, and may be induced by various kinds of compound...
  94. ncbi Antillatoxin B, a neurotoxic lipopeptide from the marine cyanobacterium Lyngbya majuscula
    L M Nogle
    College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, USA
    J Nat Prod 64:983-5. 2001
    ..Its structure was deduced from 2D NMR and data comparisons with antillatoxin. Antillatoxin B exhibited significant sodium channel-activating (EC(50) = 1.77 microM) and ichthyotoxic (LC(50) = 1 microM) properties...
  95. ncbi Manauealides, some of the causative agents of a red alga Gracilaria coronopifolia poisoning in Hawaii
    H Nagai
    Suntory Institute for Bioorganic Research, Osaka, Japan
    J Nat Prod 60:925-8. 1997
    ..Compounds 1 and 2 are presumed to be the causative toxins of G. coronopifolia food poisoning in Hawaii. Manauealide A (1) and C (3) are new macrolides, whereas manauealide B (2) is a known semisynthetic product of 5...
  96. ncbi Characterization of the preferred stereochemistry for the neuropharmacologic actions of antillatoxin
    W I Li
    Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602 7389, USA
    J Nat Prod 67:559-68. 2004
    ..The decreased potency of the three non-naturally occurring antillatoxin stereoisomers is certainly a result of their dramatically altered overall molecular topologies...
  97. ncbi Patterns of glycosidases in the histiocytic cell line U-937. Effects of agents inducing cell differentiation
    U Bjare
    National Bacteriological Laboratory, Stockholm, Sweden
    Int J Biochem 20:1291-8. 1988
    ..5. Alterations have been monitored as relative effects upon the absolute glycosidase activities and as effects upon selected ratios of different glycosidases. 6. The separate inducing agents show distinct enzyme patterns...
  98. ncbi Differential stimulation of mononuclear phagocyte IL 1 production and oxidative burst by tumor-promoting and non-tumor-promoting agents
    R N Apte
    Unit of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
    Immunobiology 175:470-81. 1987
    ..The afore-described findings lend support to the idea that chronic inflammatory phagocytes might play a role in the tumor promoting process by furnishing both carcinogenic and growth factors at the site of tumor origin...
  99. ncbi Tumour promoters/protein-kinase C activators augment the survival and function of human monocyte-derived macrophages in long-term cultures
    S Markovich
    Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Israel
    Scand J Immunol 39:39-44. 1994
    ..PKC activators/tumour promoters augmented the viability of long-term cultures of human monocyte-derived macrophages. Such macrophages may facilitate cell and molecular biology studies of differentiated human macrophages...
  100. ncbi Anti-cancer effects of morphine through inhibition of tumour necrosis factor-alpha release and mRNA expression
    N Sueoka
    Saitama Cancer Center Research Institute, Ina, Kitaadachi gun, Japan
    Carcinogenesis 17:2337-41. 1996
    ..The high dosage of morphine required to induce anticarcinogenic effects is also discussed...
  101. ncbi Protein kinase C. Modeling of the binding site and prediction of binding constants
    S Wang
    Laboratory of Medicinal Chemistry, DCT, National Cancer Institute, NIH, Bethesda, Maryland 20892
    J Med Chem 37:1326-38. 1994
    ....