gossypol

Summary

Summary: A dimeric sesquiterpene found in cottonseed (GOSSYPIUM). The (-) isomer is active as a male contraceptive (CONTRACEPTIVE AGENTS, MALE) whereas toxic symptoms are associated with the (+) isomer.

Top Publications

  1. Mao Y, Cai W, Wang J, Hong G, Tao X, Wang L, et al. Silencing a cotton bollworm P450 monooxygenase gene by plant-mediated RNAi impairs larval tolerance of gossypol. Nat Biotechnol. 2007;25:1307-13 pubmed publisher
    ..armigera), which permits this herbivore to tolerate otherwise inhibitory concentrations of the cotton metabolite, gossypol. CYP6AE14 is highly expressed in the midgut and its expression correlates with larval growth when gossypol is ..
  2. Macoska J, Adsule S, Tantivejkul K, Wang S, Pienta K, Lee C. -(-)Gossypol promotes the apoptosis of bladder cancer cells in vitro. Pharmacol Res. 2008;58:323-31 pubmed publisher
    ..In this study, we investigated whether the cottonseed polyphenol, -(-)gossypol, a BH3 mimetic, can reduce the expression of pro-survival, or increase the expression of pro-apoptotic, Bcl2 ..
  3. Cengiz E, Karaca B, Kucukzeybek Y, Gorumlu G, Gul M, Erten C, et al. Overcoming drug resistance in hormone- and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination. Mol Biol Rep. 2010;37:1269-77 pubmed publisher
    Drug resistance is a significant challenge of daily oncology practice. Docetaxel and gossypol both have antitumoral activity in hormone-refractory prostate cancer (HRPC)...
  4. Varadarajan S, Bampton E, Smalley J, Tanaka K, Caves R, Butterworth M, et al. A novel cellular stress response characterised by a rapid reorganisation of membranes of the endoplasmic reticulum. Cell Death Differ. 2012;19:1896-907 pubmed publisher
    ..Thus, ER membrane reorganisation is a feature of a new cellular stress pathway, clearly distinct from the UPR, with important consequences affecting the normal functioning of the ER. ..
  5. Przybylski P, Pyta K, Stefanska J, Ratajczak Sitarz M, Katrusiak A, Huczyński A, et al. Synthesis, crystal structures and antibacterial activity studies of aza-derivatives of phytoalexin from cotton plant--gossypol. Eur J Med Chem. 2009;44:4393-403 pubmed publisher
    Using Gossypol (GOS) extracted from cotton seeds, a series of its Schiff bases (1-18) and hydrazones (19-27) have been synthesized and evaluated for their antimicrobial activities against Gram-positive bacteria, Gram-negative bacteria and ..
  6. Oliver C, Miranda M, Shangary S, Land S, Wang S, Johnson D. (-)-Gossypol acts directly on the mitochondria to overcome Bcl-2- and Bcl-X(L)-mediated apoptosis resistance. Mol Cancer Ther. 2005;4:23-31 pubmed
    ..Thus, these proteins represent attractive targets for novel anticancer agents. The small molecule, gossypol, was initially investigated as a contraceptive agent, but subsequently has been shown to possess anticancer ..
  7. Chien C, Ko C, Shen S, Yang L, Chen Y. The role of COX-2/PGE2 in gossypol-induced apoptosis of colorectal carcinoma cells. J Cell Physiol. 2012;227:3128-37 pubmed publisher
    Our previous study showed that gossypol (GOS) exhibits potent cytotoxic effects via apoptosis induction against human colorectal carcinoma cells; however, the role of cyclooxygenase (COX)-2/prostaglandin (PG)E(2) on GOS-induced apoptosis ..
  8. Hassan M, Smith G, Ott R, Faulkner D, Firkins L, Ehrhart E, et al. Reversibility of the reproductive toxicity of gossypol in peripubertal bulls. Theriogenology. 2004;61:1171-9 pubmed
    b>Gossypol has been shown to impair sperm production in male ruminants. The purpose of this study was to determine if the adverse effects of gossypol on spermatogenesis in peripubertal bulls were reversible...
  9. Cui G, Xu Z, Yang Z, Xu Y, Xue S. A combined regimen of gossypol plus methyltestosterone and ethinylestradiol as a contraceptive induces germ cell apoptosis and expression of its related genes in rats. Contraception. 2004;70:335-42 pubmed
    Attempts to develop gossypol and steroidal hormones alone as a male contraceptive have been tested for many years; however, both caused undesirable side effects that have prevented their acceptance...

More Information

Publications97

  1. Hou D, Uto T, Tong X, Takeshita T, Tanigawa S, Imamura I, et al. Involvement of reactive oxygen species-independent mitochondrial pathway in gossypol-induced apoptosis. Arch Biochem Biophys. 2004;428:179-87 pubmed
    b>Gossypol is a component present in cottonseeds and has been demonstrated to be an effective contraceptive drug in preventing spermatogenesis in mammalian species...
  2. Stipanovic R, Lopez J, Dowd M, Puckhaber L, Duke S. Effect of racemic and (+)- and (-)-gossypol on the survival and development of Helicoverpa zea larvae. J Chem Ecol. 2006;32:959-68 pubmed
    b>Gossypol is a sesquiterpene that occurs naturally in seed and other parts of the cotton plant...
  3. Lin J, Wu Y, Yang D, Zhao Y. Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo. Oncol Rep. 2013;30:731-8 pubmed publisher
    b>Gossypol is a naturally occurring polyphenolic compound extracted from cotton plants. Recent studies revealed that gossypol is a non-peptidic small molecule inhibitor of Bcl-2/Bcl-xl...
  4. Volate S, Kawasaki B, Hurt E, Milner J, Kim Y, White J, et al. Gossypol induces apoptosis by activating p53 in prostate cancer cells and prostate tumor-initiating cells. Mol Cancer Ther. 2010;9:461-70 pubmed publisher
    ..Recent studies suggest that gossypol, a bioactive phytochemical produced by cotton plants, is a promising agent against prostate cancer...
  5. Liu G, Kelly W, Wilding G, Leopold L, Brill K, Somer B. An open-label, multicenter, phase I/II study of single-agent AT-101 in men with castrate-resistant prostate cancer. Clin Cancer Res. 2009;15:3172-6 pubmed publisher
    ..Further investigation of AT-101 in prostate cancer is warranted and trials combining AT-101 with androgen deprivation, as well as with docetaxel chemotherapy are ongoing. ..
  6. Huang Y, Wang L, Chang H, Ye W, Sugimoto Y, Dowd M, et al. Effects of serum on (-)-gossypol-suppressed growth in human prostate cancer cells. Anticancer Res. 2006;26:3613-20 pubmed
    b>Gossypol, a natural polyphenolic compound present in cottonseeds, possesses antiproliferative and pro-apoptotic effects in in vivo and in vitro models...
  7. Etxebarria A, Landeta O, Antonsson B, Basañez G. Regulation of antiapoptotic MCL-1 function by gossypol: mechanistic insights from in vitro reconstituted systems. Biochem Pharmacol. 2008;76:1563-76 pubmed publisher
    ..Accumulating evidence indicates that the natural product gossypol and its derivatives can kill tumor cells by targeting antiapoptotic BCL-2 family members in such a manner as to ..
  8. Song B, Huang G, Tong C, Li G, Wang Z, Xiong Y, et al. Gossypol suppresses mouse T lymphocytes via inhibition of NF?B, NFAT and AP-1 pathways. Immunopharmacol Immunotoxicol. 2013;35:615-21 pubmed publisher
    b>Gossypol is a kind of yellow polyphenolic compounds extracted from root stem and seed of the cotton plant. In the present study, we investigated its immunosuppressive mechanism by using BALB/c mouse T lymphocytes in vitro...
  9. Sunilkumar G, Campbell L, Puckhaber L, Stipanovic R, Rathore K. Engineering cottonseed for use in human nutrition by tissue-specific reduction of toxic gossypol. Proc Natl Acad Sci U S A. 2006;103:18054-9 pubmed
    ..for half a billion people per year; however, it is woefully underutilized because of the presence of toxic gossypol within seed glands...
  10. Lei X, Chen Y, Du G, Yu W, Wang X, Qu H, et al. Gossypol induces Bax/Bak-independent activation of apoptosis and cytochrome c release via a conformational change in Bcl-2. FASEB J. 2006;20:2147-9 pubmed
    ..One of these was gossypol, a polyphenolic compound naturally found in cottonseed that has been used in antifertility trials...
  11. Wang X, Howell C, Chen F, Yin J, Jiang Y. Gossypol--a polyphenolic compound from cotton plant. Adv Food Nutr Res. 2009;58:215-63 pubmed publisher
    b>Gossypol (C(30)H(30)O(8)) is a polyphenolic compound derived from the cotton plant (genus Gossypium, family Malvaceae). The presence of six phenolic hydroxyl groups and two aldehydic groups makes gossypol chemically reactive...
  12. Loberg R, McGregor N, Ying C, Sargent E, Pienta K. In vivo evaluation of AT-101 (R-(-)-gossypol acetic acid) in androgen-independent growth of VCaP prostate cancer cells in combination with surgical castration. Neoplasia. 2007;9:1030-7 pubmed
    ..Here, we investigated the efficacy of AT-101 (R-(-)-gossypol acetic acid; a pan small molecule inhibitor of Bcl-2, Bcl-x(L), and Mcl-1) in combination with surgical ..
  13. Yang X, Sun J, Guo J, Weng X. Identification and proteomic analysis of a novel gossypol-degrading fungal strain. J Sci Food Agric. 2012;92:943-51 pubmed publisher
    ..source of feed raw materials, has limited use in the feed industry because of the presence of the highly toxic gossypol. The aim of the current work was to isolate the gossypol-degrading fungus from a soil microcosm and investigate ..
  14. McGregor N, Patel L, Craig M, Weidner S, Wang S, Pienta K. AT-101 (R-(-)-gossypol acetic acid) enhances the effectiveness of androgen deprivation therapy in the VCaP prostate cancer model. J Cell Biochem. 2010;110:1187-94 pubmed publisher
    ..b>Gossypol, a small molecule inhibitor of pro-survival Bcl-2 family proteins, has been demonstrated to inhibit AI prostate ..
  15. Kitada S, Leone M, Sareth S, Zhai D, Reed J, Pellecchia M. Discovery, characterization, and structure-activity relationships studies of proapoptotic polyphenols targeting B-cell lymphocyte/leukemia-2 proteins. J Med Chem. 2003;46:4259-64 pubmed
    ..assays, and cell-based assays, we have begun to unravel the mechanisms of actions of certain polyphenols such as Gossypol (a compound from cotton seed extracts) and Purpurogallin (a natural compound extracted from Quercus sp...
  16. Orth R, Head G, Mierkowski M. Determining larval host plant use by a polyphagous lepidopteran through analysis of adult moths for plant secondary metabolites. J Chem Ecol. 2007;33:1131-48 pubmed
    ..for plant secondary metabolites, specifically cotinine and gossypol, which are diagnostic for larval feeding on tobacco and cotton, respectively...
  17. Ligueros M, Jeoung D, Tang B, Hochhauser D, Reidenberg M, Sonenberg M. Gossypol inhibition of mitosis, cyclin D1 and Rb protein in human mammary cancer cells and cyclin-D1 transfected human fibrosarcoma cells. Br J Cancer. 1997;76:21-8 pubmed
    The antiproliferative effects of gossypol on human MCF-7 mammary cancer cells and cyclin D1-transfected HT-1060 human fibrosarcoma cells were investigated by cell cycle analysis and effects on the cell cycle regulatory proteins Rb and ..
  18. Jiang J, Ye W, Lin Y. Gossypol inhibits the growth of MAT-LyLu prostate cancer cells by modulation of TGFbeta/Akt signaling. Int J Mol Med. 2009;24:69-75 pubmed
    b>Gossypol (GP), a male contraceptive compound naturally present in cottonseed products, possesses anti-proliferative and anti-metastatic effects in vitro and in vivo...
  19. Basini G, Bussolati S, Baioni L, Grasselli F. Gossypol, a polyphenolic aldehyde from cotton plant, interferes with swine granulosa cell function. Domest Anim Endocrinol. 2009;37:30-6 pubmed publisher
    b>Gossypol is a polyphenol isolated from the seed, roots and stem of cotton plant (Gossypium sp...
  20. Coutinho E. Gossypol: a contraceptive for men. Contraception. 2002;65:259-63 pubmed
    b>Gossypol is a polyphenol isolated from the seed, roots, and stem of the cotton plant (Gossypium sp.). The substance, a yellow pigment similar to flavonoids, is present in cottonseed oil...
  21. Li Z, Jiang W, Zhu Z, Zhu X, Zhou J, Liu Z, et al. Synergistic cytotoxicity of Bcl-xL inhibitor, gossypol and chemotherapeutic agents in non-Hodgkin's lymphoma cells. Cancer Biol Ther. 2008;7:51-60 pubmed
    ..b>Gossypol, an orally-active polyphenolic aldehyde derived from the cotton plant, has been known to have potential anti-..
  22. Bauer J, Trask D, Kumar B, Los G, Castro J, Lee J, et al. Reversal of cisplatin resistance with a BH3 mimetic, (-)-gossypol, in head and neck cancer cells: role of wild-type p53 and Bcl-xL. Mol Cancer Ther. 2005;4:1096-104 pubmed
    ..We tested a small-molecule BH3 mimetic, (-)-gossypol, which binds to the BH3 domain of Bcl-2 and Bcl-x(L), for activity against the parental and cisplatin-resistant ..
  23. Varol U, Karaca B, Tunali D, Degirmenci M, Cirak Y, Purcu D, et al. The effect of racemic gossypol and at-101 on angiogenic profile of ovcar-3 cells: a preliminary molecular framework for gossypol enantiomers. Exp Oncol. 2009;31:220-5 pubmed
    To compare the effect of racemic gossypol with its (-)/(-) enantiomer (AT-101) on expression profiles of angiogenic molecules by mRNA levels in human ovarian cancer cell line OVCAR-3...
  24. Sahin F, Avci C, Gunduz C, Sezgin C, Simsir I, Saydam G. Gossypol exerts its cytotoxic effect on HL-60 leukemic cell line via decreasing activity of protein phosphatase 2A and interacting with human telomerase reverse transcriptase activity. Hematology. 2010;15:144-50 pubmed publisher
    In this study, we aimed to investigate the potential relationship between gossypol-induced cytotoxicity of human promyelocytic leukemia cell line (HL-60) leukemic cells and intracellular serine/threonine protein phosphatase (PP) dynamics ..
  25. Gao P, Bauvy C, Souquere S, Tonelli G, Liu L, Zhu Y, et al. The Bcl-2 homology domain 3 mimetic gossypol induces both Beclin 1-dependent and Beclin 1-independent cytoprotective autophagy in cancer cells. J Biol Chem. 2010;285:25570-81 pubmed publisher
    b>Gossypol, a natural Bcl-2 homology domain 3 mimetic compound isolated from cottonseeds, is currently being evaluated in clinical trials...
  26. Barba Barajas M, Hernandez Flores G, Lerma Diaz J, Ortiz Lazareno P, Dominguez Rodriguez J, Barba Barajas L, et al. Gossypol induced apoptosis of polymorphonuclear leukocytes and monocytes: involvement of mitochondrial pathway and reactive oxygen species. Immunopharmacol Immunotoxicol. 2009;31:320-30 pubmed publisher
    The aim of this study was to determine how gossypol affects the viability and activity of polymorphonuclear leukocytes and monocytes in blood obtained from healthy donors...
  27. Gao W, Long L, Zhu L, Xu L, Gao W, Sun L, et al. Proteomic and virus-induced gene silencing (VIGS) Analyses reveal that gossypol, brassinosteroids, and jasmonic acid contribute to the resistance of cotton to Verticillium dahliae. Mol Cell Proteomics. 2013;12:3690-703 pubmed publisher
    ..Based on the results, we suggest that the production of gossypol is sufficient to affect the cotton resistance to V. dahliae...
  28. Hsiao W, Tsai M, Jow G, Tien L, Lee Y. Involvement of Smac, p53, and caspase pathways in induction of apoptosis by gossypol in human retinoblastoma cells. Mol Vis. 2012;18:2033-42 pubmed
    ..More effective treatments are therefore imperative. Gossypol has been reported as a potential inhibitor of cell proliferation in various types of cancers, such as prostate ..
  29. Yildirim Aksoy M, Lim C, Dowd M, Wan P, Klesius P, Shoemaker C. In vitro inhibitory effect of gossypol from gossypol-acetic acid, and (+)- and (-)-isomers of gossypol on the growth of Edwardsiella ictaluri. J Appl Microbiol. 2004;97:87-92 pubmed
    This study was conducted to evaluate the toxic effect of gossypol from gossypol-acetic acid, and (+)- and (-)-isomers of gossypol on the growth of Edwardsiella ictaluri.
  30. Uzunoglu S, Karaca B, Atmaca H, Kisim A, Sezgin C, Karabulut B, et al. Comparison of XTT and Alamar blue assays in the assessment of the viability of various human cancer cell lines by AT-101 (-/- gossypol). Toxicol Mech Methods. 2010;20:482-6 pubmed publisher
  31. Wei J, Kitada S, Stebbins J, Placzek W, Zhai D, Wu B, et al. Synthesis and biological evaluation of Apogossypolone derivatives as pan-active inhibitors of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins. J Med Chem. 2010;53:8000-11 pubmed publisher
    ..Together with its negligible toxicity, compound 6f represents a promising drug lead for the development of novel apoptosis-based therapies for cancer. ..
  32. Moon D, Kim M, Lee J, Kim G. Gossypol suppresses NF-kappaB activity and NF-kappaB-related gene expression in human leukemia U937 cells. Cancer Lett. 2008;264:192-200 pubmed publisher
    Recent studies indicate that gossypol possesses potent antitumor activities in vitro and in vivo. The nuclear factor-kappa B (NF-kappaB) plays an important role in tumor cell growth, proliferation, invasion, and survival...
  33. Sprogøe K, Staek D, Ziegler H, Jensen T, Holm Møller S, Jaroszewski J. Combining HPLC-PDA-MS-SPE-NMR with circular dichroism for complete natural product characterization in crude extracts: levorotatory gossypol in Thespesia danis. J Nat Prod. 2008;71:516-9 pubmed publisher
    ..Thus, use of HPLC-PDA-MS-SPE-NMR in combination with CD allowed rapid detection of ( R)-(-)-gossypol [( R)- 1] in Thespesia danis, providing a very rare example of the predominance of the levorotatory enantiomer of ..
  34. Yuan Y, Tang A, Castoreno A, Kuo S, Wang Q, Kuballa P, et al. Gossypol and an HMT G9a inhibitor act in synergy to induce cell death in pancreatic cancer cells. Cell Death Dis. 2013;4:e690 pubmed publisher
    ..The natural product and putative BH3 mimetic gossypol enhanced the cytotoxicity of BRD4770 in a synergistic manner in p53-mutant PANC-1 cells but not in immortalized ..
  35. Kitada S, Kress C, Krajewska M, Jia L, Pellecchia M, Reed J. Bcl-2 antagonist apogossypol (NSC736630) displays single-agent activity in Bcl-2-transgenic mice and has superior efficacy with less toxicity compared with gossypol (NSC19048). Blood. 2008;111:3211-9 pubmed publisher
    ..In this study, we compared the toxicity and efficacy in mice of natural product gossypol and its semisynthetic derivative apo-gossypol, compounds that bind and inhibit antiapoptotic Bcl-2 family ..
  36. Jiang J, Slivova V, Jedinak A, Sliva D. Gossypol inhibits growth, invasiveness, and angiogenesis in human prostate cancer cells by modulating NF-?B/AP-1 dependent- and independent-signaling. Clin Exp Metastasis. 2012;29:165-78 pubmed publisher
    Although previous studies demonstrated anticancer activities of gossypol through the induction of apoptosis, the molecular mechanism(s) responsible for the inhibitory effects of gossypol on the metastatic behavior of cancer cells remain ..
  37. Ouyang D, Ji Y, Saltis M, Xu L, Zhang Y, Zha Q, et al. Valproic acid synergistically enhances the cytotoxicity of gossypol in DU145 prostate cancer cells: an iTRTAQ-based quantitative proteomic analysis. J Proteomics. 2011;74:2180-93 pubmed publisher
    b>Gossypol (GOS), a BH3 mimetic, has been investigated as a sensitizing co-therapy to radiation and chemotherapy in treatment of metastatic prostate cancer...
  38. Van Poznak C, Seidman A, Reidenberg M, Moasser M, Sklarin N, Van Zee K, et al. Oral gossypol in the treatment of patients with refractory metastatic breast cancer: a phase I/II clinical trial. Breast Cancer Res Treat. 2001;66:239-48 pubmed
    b>Gossypol has demonstrated in vitro effects on cell cycle regulation and anti-tumor activity against mammary carcinoma cell lines...
  39. Romualdo G, Klinefelter G, de K. Postweaning exposure to gossypol results in epididymis-specific effects throughout puberty and adulthood in rats. J Androl. 2002;23:220-8 pubmed
    b>Gossypol, a yellow pigment found in cottonseeds, well known for its antifertility properties in animals, has been used as a contraceptive by men...
  40. Huang Y, Wang L, Chang H, Ye W, Dowd M, Wan P, et al. Molecular mechanisms of (-)-gossypol-induced apoptosis in human prostate cancer cells. Anticancer Res. 2006;26:1925-33 pubmed
    b>Gossypol, a natural compound present in cottonseeds, displays antiproliferative and pro-apoptotic effects against various cancer cells. The (-)-gossypol enantiomer is a more potent inhibitor of cancer cell growth...
  41. Du L, Ge F, Zhu S, Parajulee M. Effect of cotton cultivar on development and reproduction of Aphis gossypii (Homoptera: Aphididae) and its predator Propylaea japonica (Coleoptera: Coccinellidae). J Econ Entomol. 2004;97:1278-83 pubmed
    The effects of three cotton cultivars with low ('ZMZ13'), medium ('HZ401'), and high ('M9101') gossypol contents on the development, reproduction, and survival of Aphis gossypii Glover and its predator Propylaea japonica (Thunberg) were ..
  42. Carriere Y, Ellers Kirk C, Biggs R, Higginson D, Dennehy T, Tabashnik B. Effects of gossypol on fitness costs associated with resistance to Bt cotton in pink bollworm. J Econ Entomol. 2004;97:1710-8 pubmed
    ..Specifically, we tested the hypotheses that gossypol affects the magnitude or dominance of fitness costs, by measuring performance of three independent sets of pink ..
  43. Mohammad R, Wang S, Banerjee S, Wu X, Chen J, Sarkar F. Nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-XL, (-)-Gossypol, enhances biological effect of genistein against BxPC-3 human pancreatic cancer cell line. Pancreas. 2005;31:317-24 pubmed
    ..b>Gossypol, a natural polyphenolic compound isolated from cottonseeds, is a dual and potent small-molecule inhibitor of Bcl-..
  44. Yurtcu E, Ergun M, Menevse A. Apoptotic effect of gossypol on human lymphocytes. Cell Biol Int. 2003;27:791-4 pubmed
    The overall objective of this study was to determine the effect of gossypol on human lymphocytes. Blood samples were taken from healthy donors and lymphocytes were cultured with various concentrations of gossypol (25-150 microM)...
  45. Deoras D, Young Curtis P, Dalvi R, Tippett F. Effect of gossypol on hepatic and serum gamma-glutamyltransferase activity in rats. Vet Res Commun. 1997;21:317-23 pubmed
    A single intraperitoneal dose (25 mg/kg) of gossypol given to male Sprague-Dawley rats caused marked changes in the activity of the hepatic and serum gamma-glutamyltransferase (GGT) and microsomal monooxygenases...
  46. Vander Jagt D, Deck L, Royer R. Gossypol: prototype of inhibitors targeted to dinucleotide folds. Curr Med Chem. 2000;7:479-98 pubmed
    b>Gossypol, a disesquiterpene from cottonseed, exhibits multiple biological properties, including male antifertility activity and anticancer activity...
  47. Fonseca N, Gadelha I, Oloris S, Soto Blanco B. Effectiveness of albumin-conjugated gossypol as an immunogen to prevent gossypol-associated acute hepatotoxicity in rats. Food Chem Toxicol. 2013;56:149-53 pubmed publisher
    b>Gossypol is a highly reactive compound present in cotton (Gossypium spp.)...
  48. Jan C, Lin M, Chou K, Huang J. Novel effects of gossypol, a chemical contraceptive in man: mobilization of internal Ca(2+) and activation of external Ca(2+) entry in intact cells. Biochim Biophys Acta. 2000;1496:270-6 pubmed
    The effect of gossypol on Ca(2+) signaling in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe...
  49. Le Blanc M, Russo J, Kudelka A, Smith J. An in vitro study of inhibitory activity of gossypol, a cottonseed extract, in human carcinoma cell lines. Pharmacol Res. 2002;46:551-5 pubmed
    b>Gossypol, a cottonseed extract, has been shown to have antiproliferative activity in a variety of cancer cell lines. The objective of this study was to determine the inhibitory effects of gossypol on cell proliferation...
  50. Yan F, Cao X, Jiang H, Zhao X, Wang J, Lin Y, et al. A novel water-soluble gossypol derivative increases chemotherapeutic sensitivity and promotes growth inhibition in colon cancer. J Med Chem. 2010;53:5502-10 pubmed publisher
    Compound 1 ((-)-gossypol) has been long known as a chemical anticancer agent. With its low water solubility and toxicity, it is not widely used as a commercial drug...
  51. Turco E, Vizzuso C, Franceschini S, Ragazzi A, Stefanini F. The in vitro effect of gossypol and its interaction with salts on conidial germination and viability of Fusarium oxysporum sp. vasinfectum isolates. J Appl Microbiol. 2007;103:2370-81 pubmed
    To assess the effect of different concentrations of gossypol (0, 2, 4, 10 and 20 mg l(-1)) in combination with NaCl and Na(2)SO(4) (20 mS cm(-1)) on the conidial germination and viability of Fusarium oxysporum f.sp. vasinfectum (Fov)...
  52. Hernández Cerón J, Jousan F, Soto P, Hansen P. Timing of inhibitory actions of gossypol on cultured bovine embryos. J Dairy Sci. 2005;88:922-8 pubmed
    Culture of bovine preimplantation embryos with gossypol, a polyphenolic pigment in cottonseed, inhibits development. Neither stage at which embryos are most sensitive to gossypol, nor the mechanism by which development is blocked is known...
  53. Wang X, Beckham T, Morris J, Chen F, Gangemi J. Bioactivities of gossypol, 6-methoxygossypol, and 6,6'-dimethoxygossypol. J Agric Food Chem. 2008;56:4393-8 pubmed publisher
    ..Together with gossypol, these natural products were investigated for a wide range of bioactivities...
  54. Villasenor M, Coscioni A, Galvao K, Chebel R, Santos J. Gossypol disrupts embryo development in heifers. J Dairy Sci. 2008;91:3015-24 pubmed publisher
    Our objectives were to determine the effects of dietary free gossypol (FG) intake on plasma and uterine gossypol concentrations and embryo development and viability before and after culture with gossypol...
  55. Zhang W, Xu Z, Zhao S, Jiang J, Wang Y, Yan X. Optimization of process parameters for reduction of gossypol levels in cottonseed meal by Candida tropicalis ZD-3 during solid substrate fermentation. Toxicon. 2006;48:221-6 pubmed
    The objective of this work is to optimize the process parameters for detoxification of gossypol in cottonseed meal (CSM) by Candida tropicalis ZD-3 during solid substrate fermentation (SSF)...
  56. Hu Z, Wang J, Cheng G, Zhu X, Huang P, Yang D, et al. Apogossypolone targets mitochondria and light enhances its anticancer activity by stimulating generation of singlet oxygen and reactive oxygen species. Chin J Cancer. 2011;30:41-53 pubmed
    Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells...
  57. Pang X, Wu Y, Wu Y, Lu B, Chen J, Wang J, et al. (-)-Gossypol suppresses the growth of human prostate cancer xenografts via modulating VEGF signaling-mediated angiogenesis. Mol Cancer Ther. 2011;10:795-805 pubmed publisher
    b>Gossypol, a natural BH3-mimetic and small-molecule Bcl-2 inhibitor, shows promise in ongoing phase II clinical trials for human cancers...
  58. Zhang X, Huang X, Hu X, Zhan Y, An Q, Yang S, et al. Apogossypolone, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces autophagy of PC-3 and LNCaP prostate cancer cells in vitro. Asian J Androl. 2010;12:697-708 pubmed publisher
    Limited treatment options are available for aggressive prostate cancer. Gossypol has been reported to have a potent anticancer activity in many types of cancer...
  59. Chang Q, Liu Z, Ma W, Hei C, Shen X, Qian X, et al. Drug synergistic antifertility effect of combined administration of low-dose gossypol with steroid hormones in rats. Chin Med J (Engl). 2011;124:1678-82 pubmed
    Our previous studies suggested that low-dose gossypol combined with steroid hormones has a reversible antifertility role in adult male rats, and the course of treatment was shorter than that of either gossypol or steroid hormones alone...
  60. Liu S, Kulp S, Sugimoto Y, Jiang J, Chang H, Dowd M, et al. The (-)-enantiomer of gossypol possesses higher anticancer potency than racemic gossypol in human breast cancer. Anticancer Res. 2002;22:33-8 pubmed
    Natural gossypol (GP), a polyphenolic pigment in cottonseed, is a racemic mixture of two enantiomers, (+)GP and (-)GP...
  61. Ergun M, Konac E, Erbas D, Ekmekci A. Apoptosis and nitric oxide release induced by thalidomide, gossypol and dexamethasone in cultured human chronic myelogenous leukemic K-562 cells. Cell Biol Int. 2004;28:237-42 pubmed
    The effects of different dosages of thalidomide, gossypol and dexamethasone on the levels of apoptosis and nitric oxide (NO) production were studied in a human chronic myelogenous leukemic cell line, K-562...
  62. Benedict C, Liu J, Stipanovic R. The peroxidative coupling of hemigossypol to (+)- and (-)-gossypol in cottonseed extracts. Phytochemistry. 2006;67:356-61 pubmed
    ..Texas Marker 1 catalyzed a bimolecular coupling of [4-(3)H]-hemigossypol to [4,4'-(3)H(2)]-gossypol. The reaction was dependent on the addition of H(2)O(2) and was inhibited 71-94% by 1 and 10mM sodium azide...
  63. El Mokadem M, Taha T, Samak M, Yassen A. Alleviation of reproductive toxicity of gossypol using selenium supplementation in rams. J Anim Sci. 2012;90:3274-85 pubmed publisher
    The objective of this study was to evaluate the reproductive toxicity of gossypol and the possible counteracting effect of selenium supplementation in rams...
  64. Akinola O, Dosunmu O, Dini L, Ajayi S. Proteinaceous diet inhibits gossypol-induced spermatotoxicity. Eur J Histochem. 2006;50:205-8 pubmed
    The present study was designed to investigate the effect of a proteinaceous dietary supplement, fishmeal, on gossypol-induced spermatotoxicity. Twenty-five adult male Wistar rats, averaging 205 g b.w...
  65. Badawy S, Souid A, Cuenca V, Montalto N, Shue F. Gossypol inhibits proliferation of endometrioma cells in culture. Asian J Androl. 2007;9:388-93 pubmed
    To evaluate the anti-proliferative activity and mitochondrial toxicity of gossypol in endometrioma cells maintained in short-term cultures...
  66. Tao X, Xue X, Huang Y, Chen X, Mao Y. Gossypol-enhanced P450 gene pool contributes to cotton bollworm tolerance to a pyrethroid insecticide. Mol Ecol. 2012;21:4371-85 pubmed publisher
    Cotton plants accumulate phytotoxins, including gossypol and related sesquiterpene aldehydes, to resist insect herbivores and pathogens...
  67. Dash R, Azab B, Quinn B, Shen X, Wang X, Das S, et al. Apogossypol derivative BI-97C1 (Sabutoclax) targeting Mcl-1 sensitizes prostate cancer cells to mda-7/IL-24-mediated toxicity. Proc Natl Acad Sci U S A. 2011;108:8785-90 pubmed publisher
  68. Coutinho E, Athayde C, Atta G, Gu Z, Chen Z, Sang G, et al. Gossypol blood levels and inhibition of spermatogenesis in men taking gossypol as a contraceptive. A multicenter, international, dose-finding study. Contraception. 2000;61:61-7 pubmed
    The safety and efficacy of gossypol continues to be controversial. The aim of this study was to evaluate gossypol as a contraceptive pill for men at doses lower than those previously prescribed and in men from various ethnic origin...
  69. Xu L, Yang D, Wang S, Tang W, Liu M, Davis M, et al. (-)-Gossypol enhances response to radiation therapy and results in tumor regression of human prostate cancer. Mol Cancer Ther. 2005;4:197-205 pubmed
    ..b>Gossypol, a natural polyphenol product from cottonseed, has recently been identified as a potent small molecule inhibitor ..
  70. Mellon J, Zelaya C, Dowd M. Inhibitory effects of gossypol-related compounds on growth of Aspergillus flavus. Lett Appl Microbiol. 2011;52:406-12 pubmed publisher
    The objective of this study was to test a series of gossypol-related compounds for growth inhibition against Aspergillus flavus.
  71. Mohammad R, Wang S, Aboukameel A, Chen B, Wu X, Chen J, et al. Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-X(L) [(-)-gossypol] against diffuse large cell lymphoma. Mol Cancer Ther. 2005;4:13-21 pubmed
    ..Diffuse large cell lymphoma (DLCL) is the most common subtype of non-Hodgkin's lymphoma. (-)-Gossypol, a natural product isolated from cottonseeds, was discovered as a potent small-molecule inhibitor of Bcl-2 and ..
  72. Karaca B, Kucukzeybek Y, Gorumlu G, Erten C, Gul M, Cengiz E, et al. Profiling of angiogenic cytokines produced by hormone- and drug-refractory prostate cancer cell lines, PC-3 and DU-145 before and after treatment with gossypol. Eur Cytokine Netw. 2008;19:176-84 pubmed publisher
    ..We also studied the effect of gossypol, a natural polyphenolic cotton-seed extract, on the angiogenic cytokine profile of these cell lines...
  73. Xu P, Ye W, Jen R, Lin S, Kuo C, Lin Y. Mitogenic activity of zeranol in human breast cancer cells is enhanced by leptin and suppressed by gossypol. Anticancer Res. 2009;29:4621-8 pubmed
    ..Zeranol is used as an anabolic growth promoter to stimulate cattle growth in the U.S. beef industry. (-)-Gossypol, a natural polyphenolic compound extracted from cottonseed, is an anticancer chemopreventive agent...
  74. Chang J, Hsu Y, Kuo P, Chiang L, Lin C. Upregulation of Fas/Fas ligand-mediated apoptosis by gossypol in an immortalized human alveolar lung cancer cell line. Clin Exp Pharmacol Physiol. 2004;31:716-22 pubmed
    b>Gossypol has wide antineoplastic effects in vitro, but its effects on human lung cancer have not been explored...
  75. Meng Y, Li Y, Li J, Li H, Fu J, Liu Y, et al. (-)Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells. Leuk Lymphoma. 2007;48:2204-12 pubmed
    ..b>Gossypol is a natural polyphenolic compound isolated from cottonseed and has antiproliferative activity in a variety of ..
  76. Bushunow P, Reidenberg M, Wasenko J, Winfield J, Lorenzo B, Lemke S, et al. Gossypol treatment of recurrent adult malignant gliomas. J Neurooncol. 1999;43:79-86 pubmed
    b>Gossypol, a polyphenolic compound which depletes cellular energy by inhibition of several intracellular dehydrogenases, has been shown to have antiproliferative activity against human glial tumor cell lines in vitro and in nude mouse ..
  77. Weissenmayer B, Boeckeler K, Lahrz A, Mutzel R. The calcineurin inhibitor gossypol impairs growth, cell signalling and development in Dictyostelium discoideum. FEMS Microbiol Lett. 2005;242:19-25 pubmed
    ..to pharmacologically target calcineurin activity in vivo by using the recently described calcineurin inhibitor, gossypol. Up-regulation of expression of the gene for the Ca2+-ATPase PAT1 in conditions of Ca2+ stress was reduced by ..
  78. Banerjee S, Choi M, Aboukameel A, Wang Z, Mohammad M, Chen J, et al. Preclinical studies of apogossypolone, a novel pan inhibitor of bcl-2 and mcl-1, synergistically potentiates cytotoxic effect of gemcitabine in pancreatic cancer cells. Pancreas. 2010;39:323-31 pubmed publisher
    ..Apogossypolone (ApoG2) is an analogue of (-)-gossypol, exhibiting binding activity with Ki values of 35 nmol/L for Bcl-2 and 25 nmol/L for Mcl-1...
  79. Mellon J, Zelaya C, Dowd M, Beltz S, Klich M. Inhibitory effects of gossypol, gossypolone, and apogossypolone on a collection of economically important filamentous fungi. J Agric Food Chem. 2012;60:2740-5 pubmed publisher
    Racemic gossypol and its related derivatives gossypolone and apogossypolone demonstrated significant growth inhibition against a diverse collection of filamentous fungi that included Aspergillus flavus, Aspergillus parasiticus, ..
  80. Kline M, Rajkumar S, Timm M, Kimlinger T, Haug J, Lust J, et al. R-(-)-gossypol (AT-101) activates programmed cell death in multiple myeloma cells. Exp Hematol. 2008;36:568-76 pubmed publisher
    ..R-(-)-gossypol (AT-101) is a small molecule that mimics the BH3 domain of cellular Bcl-2 inhibitors and interferes with the ..
  81. Cheng J, Lo Y, Yeh J, Cheng H, Liu C, Chen W, et al. Effect of gossypol on intracellular Ca2+ regulation in human hepatoma cells. Chin J Physiol. 2003;46:117-22 pubmed
    b>Gossypol is a natural toxicant present in cottonseeds, and is hepatotoxic to animals and human...
  82. Keller P, Birch C, Leach S, Tyssen D, Griffith R. Novel pharmacophore-based methods reveal gossypol as a reverse transcriptase inhibitor. J Mol Graph Model. 2003;21:365-73 pubmed
    ..A notable inclusion was a series of gossypol derivatives...
  83. Velasquez Pereira J, Aréchiga C, McDowell L, Hansen P, Chenoweth P, Calhoun M, et al. Effects of gossypol from cottonseed meal and dietary vitamin E on the reproductive characteristics of superovulated beef heifers. J Anim Sci. 2002;80:2485-92 pubmed
    ..Hereford-Angus crossbred heifers (average 397 kg BW) were used to test the effect of feeding cottonseed meal (gossypol) and vitamin E on embryo quality and ovarian characteristics...
  84. Balakrishnan K, Wierda W, Keating M, Gandhi V. Gossypol, a BH3 mimetic, induces apoptosis in chronic lymphocytic leukemia cells. Blood. 2008;112:1971-80 pubmed publisher
    b>Gossypol, a cottonseed extract derivative, acts as a BH3-mimetic, binding to the BH3 pocket of antiapoptotic proteins and displacing pro-death partners to induce apoptosis...
  85. Puckhaber L, Dowd M, Stipanovic R, Howell C. Toxicity of (+)- and (-)-gossypol to the plant pathogen, Rhizoctonia solani. J Agric Food Chem. 2002;50:7017-21 pubmed
    The dimeric sesquiterpene gossypol occurs naturally in cottonseed and other parts of the cotton plant. Gossypol exists as enantiomers because of the restricted rotation around the central binaphthyl bond...
  86. Cho H, Lai T, Kwon G. Poly(ethylene glycol)-block-poly(?-caprolactone) micelles for combination drug delivery: evaluation of paclitaxel, cyclopamine and gossypol in intraperitoneal xenograft models of ovarian cancer. J Control Release. 2013;166:1-9 pubmed publisher
    ..PEG-b-PCL) micelles were loaded with paclitaxel (cytotoxic agent), cyclopamine (hedgehog inhibitor), and gossypol (Bcl-2 inhibitor)...
  87. Arnold A, Aboukameel A, Chen J, Yang D, Wang S, al Katib A, et al. Preclinical studies of Apogossypolone: a new nonpeptidic pan small-molecule inhibitor of Bcl-2, Bcl-XL and Mcl-1 proteins in Follicular Small Cleaved Cell Lymphoma model. Mol Cancer. 2008;7:20 pubmed publisher
    ..These studies suggest that ApoG2 can be an effective therapeutic agent against FL...
  88. Javed M, Khan M. Effect of amino acids on inhibition of lactate dehydrogenase-X by gossypol. Exp Mol Med. 1999;31:25-9 pubmed
    b>Gossypol acetic acid (GAA) has been shown to have male antifertility effects, but there are pronounced differences among animal species...