Summary: ISOQUINOLINES with a benzyl substituent.

Top Publications

  1. Kikukawa Y, Okuno Y, Tatetsu H, Nakamura M, Harada N, Ueno S, et al. Induction of cell cycle arrest and apoptosis in myeloma cells by cepharanthine, a biscoclaurine alkaloid. Int J Oncol. 2008;33:807-14 pubmed
    ..Although analysis of these two pathways should be clarified further, the use of CEP may be considered as a potential therapeutic agent for a subset of MM. ..
  2. Ng L, Chiang L, Lin Y, Lin C. Antiproliferative and apoptotic effects of tetrandrine on different human hepatoma cell lines. Am J Chin Med. 2006;34:125-35 pubmed
    ..The effect of TET on cell cycle progression was found to vary with the type of hepatoma cells, suggesting the genetic make-up of the cells play an important role in the response to drug treatment. ..
  3. Wu J, Chen Y, Chen J, Lin T, Tseng S. Tetrandrine induces apoptosis and growth suppression of colon cancer cells in mice. Cancer Lett. 2010;287:187-95 pubmed publisher
    ..These data suggest that tetrandrine induced significant apoptosis of cultured and subcutaneous CT-26 cells. Tetrandrine-induced apoptosis might be at least partially related to activation of the p38 MAPK signaling pathway. ..
  4. Hawkins K, Smolke C. Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae. Nat Chem Biol. 2008;4:564-73 pubmed publisher
    ..Our engineered microbial hosts offer access to a rich group of BIA molecules and associated activities that will be further expanded through synthetic chemistry and biology approaches. ..
  5. Chen J, Qi J, Chen F, Liu J, Wang T, Yang J, et al. Relaxation mechanisms of neferine on the rabbit corpus cavernosum tissue in vitro. Asian J Androl. 2007;9:795-800 pubmed
  6. Sun J, Zhang X, He Z, Gu Y, Yu Y, Fang Y, et al. [The mechanism of apoptosis of chronic myeloid leukemia cells induced by the novel p210 bcr/abl inhibitor berbamine]. Zhonghua Yi Xue Za Zhi. 2006;86:2246-51 pubmed
  7. Wang G, Zhang J, Lu Q, Xu R, Dong Q. Berbamine induces apoptosis in human hepatoma cell line SMMC7721 by loss in mitochondrial transmembrane potential and caspase activation. J Zhejiang Univ Sci B. 2007;8:248-55 pubmed
    ..The anticancer activity of berbamine could be attributed partly to its inhibition of cell proliferation and induction of apoptosis in cancer cells through loss in mitochondrial transmembrane potential and caspase activation. ..
  8. Yu V, Ho W. Tetrandrine inhibits hepatocellular carcinoma cell growth through the caspase pathway and G2/M phase. Oncol Rep. 2013;29:2205-10 pubmed publisher
    ..In addition, tetrandrine increased caspase-3 expression and induced DNA fragmentation in Huh-7 cells. The results suggest that the anti-cancer effect of tetrandrine in Huh-7 cells may be mediated by p53-independent pathways. ..
  9. Lee S, Kim H, Park J, Park J, Kim T. Metabolic engineering of microorganisms: general strategies and drug production. Drug Discov Today. 2009;14:78-88 pubmed publisher
    ..Also, systems metabolic engineering of Escherichia coli for the production of L-valine, an important drug precursor, is showcased as an important strategy of future metabolic engineering effort. ..

More Information


  1. Yang X, Jiang S, Zhang L, Liu Q, Gong P. Inhibitory effect of dauricine on inflammatory process following focal cerebral ischemia/reperfusion in rats. Am J Chin Med. 2007;35:477-86 pubmed
    ..05 or p < 0.01). These results suggest that dauricin attenuates the inflammation process induced by I/R. The neuroprotective effect of dauricine may partly due to the inhibition acute inflammation induced by I/R. ..
  2. Zhao X, He Z, Wu D, Xu R. Berbamine selectively induces apoptosis of human acute promyelocytic leukemia cells via survivin-mediated pathway. Chin Med J (Engl). 2007;120:802-6 pubmed
  3. Lee E, Facchini P. Norcoclaurine synthase is a member of the pathogenesis-related 10/Bet v1 protein family. Plant Cell. 2010;22:3489-503 pubmed publisher
    ..In our hands, Cj NCS1 did not catalyze the formation of (S)-norcoclaurine from dopamine and 4-hydroxyphenylacetaldehyde...
  4. Liu C, Tsai W, Shen C, Lin Y, Liao J, Chen C, et al. Inhibition of (S)-armepavine from Nelumbo nucifera on autoimmune disease of MRL/MpJ-lpr/lpr mice. Eur J Pharmacol. 2006;531:270-9 pubmed
    ..We suggest that (S)-armepavine may be an immunomodulator for the management of autoimmune diseases like SLE...
  5. Li X, Lu X, Xu H, Zhu Z, Yin H, Qian X, et al. Paclitaxel/tetrandrine coloaded nanoparticles effectively promote the apoptosis of gastric cancer cells based on "oxidation therapy". Mol Pharm. 2012;9:222-9 pubmed publisher
    ..The present results suggest that the codelivery of Ptx and Tet by nanoparticles provides a novel therapeutic strategy basing on "oxidation therapy" against gastric cancer. ..
  6. Shen D, Tang Q, Yan L, Zhang Y, Zhu L, Wang L, et al. Tetrandrine blocks cardiac hypertrophy by disrupting reactive oxygen species-dependent ERK1/2 signalling. Br J Pharmacol. 2010;159:970-81 pubmed publisher
    ..Taken together, our results suggest that tetrandrine can improve cardiac function and prevent the development of cardiac hypertrophy by suppressing the reactive oxygen species-dependent ERK1/2 signalling pathway. ..
  7. Cheng J, Wang J, Chen B, Xia G, Cai X, Liu R, et al. A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin. Int J Nanomedicine. 2011;6:2123-31 pubmed publisher
  8. Gong K, Chen C, Zhan Y, Chen Y, Huang Z, Li W. Autophagy-related gene 7 (ATG7) and reactive oxygen species/extracellular signal-regulated kinase regulate tetrandrine-induced autophagy in human hepatocellular carcinoma. J Biol Chem. 2012;287:35576-88 pubmed publisher
    ..elegans muscle cells. Therefore, these findings suggest that tetrandrine is a potent autophagy agonist and may be a promising clinical chemotherapeutic agent...
  9. Haginaka J, Kitabatake T, Hirose I, Matsunaga H, Moaddel R. Interaction of cepharanthine with immobilized heat shock protein 90α (Hsp90α) and screening of Hsp90α inhibitors. Anal Biochem. 2013;434:202-6 pubmed publisher
    ..Furthermore, the Hsp90α-NT column was applied for preliminary screening of natural Hsp90α inhibitors by zonal chromatography studies. ..
  10. Minami H, Kim J, Ikezawa N, Takemura T, Katayama T, Kumagai H, et al. Microbial production of plant benzylisoquinoline alkaloids. Proc Natl Acad Sci U S A. 2008;105:7393-8 pubmed publisher
  11. Chen B, Sun Q, Wang X, Gao F, Dai Y, Yin Y, et al. Reversal in multidrug resistance by magnetic nanoparticle of Fe3O4 loaded with adriamycin and tetrandrine in K562/A02 leukemic cells. Int J Nanomedicine. 2008;3:277-86 pubmed
    ..We propose that Fe3O4-MNPs loaded with ADM and Tet probably have synergetic effect on reversal in multidrug resistance. ..
  12. Cheng J, Wu W, Chen B, Gao F, Xu W, Gao C, et al. Effect of magnetic nanoparticles of Fe3O4 and 5-bromotetrandrine on reversal of multidrug resistance in K562/A02 leukemic cells. Int J Nanomedicine. 2009;4:209-16 pubmed
    ..Furthermore, the combination did not have significant cytotoxicity in PMBCs. We propose that MNPs-Fe3O4 conjugated with DNR and BrTet probably have synergetic effects on MDR reversal. ..
  13. Qian X, Yan B, Zhou X, Xie L, Wei J, Li R, et al. Synergistic antiangiogenic activity of tetrandrine combined with Endostar on the human umbilical vein endothelial cell model. Cancer Biother Radiopharm. 2013;28:385-90 pubmed publisher
    ..Thus, we identified that there was a synergistic antiangiogenic effect in vitro when combining TET with Endostar. ..
  14. Lee E, Facchini P. Tyrosine aminotransferase contributes to benzylisoquinoline alkaloid biosynthesis in opium poppy. Plant Physiol. 2011;157:1067-78 pubmed publisher
  15. Wei J, Liu B, Wang L, Qian X, Ding Y, Yu L. Synergistic interaction between tetrandrine and chemotherapeutic agents and influence of tetrandrine on chemotherapeutic agent-associated genes in human gastric cancer cell lines. Cancer Chemother Pharmacol. 2007;60:703-11 pubmed
    ..Tetrandrine appears a promising candidate for combining with three chemotherapeutic agents. The possible mechanisms might be the synergistic apoptotic effect and the downregulation of chemotherapeutic agent-associated genes. ..
  16. Zhang H, Wang K, Zhang G, Ho H, Gao A. Synergistic anti-candidal activity of tetrandrine on ketoconazole: an experimental study. Planta Med. 2010;76:53-61 pubmed publisher
    ..We conclude that noncytotoxic doses of TET synergistically enhance KCZ candidacidal activity in vitro and in vivo...
  17. Chen Y, Chen J, Tseng S. Effects of tetrandrine plus radiation on neuroblastoma cells. Anticancer Res. 2009;29:3163-71 pubmed
    ..The effect is, at least partly, related to the partial abrogation of radiation-induced G(2)/M accumulation. ..
  18. Biswas K, Tancharoen S, Tancharon S, Sarker K, Kawahara K, Hashiguchi T, et al. Cepharanthine triggers apoptosis in a human hepatocellular carcinoma cell line (HuH-7) through the activation of JNK1/2 and the downregulation of Akt. FEBS Lett. 2006;580:703-10 pubmed
  19. Xue Y, Wang Y, Feng D, Xiao B, Xu L. Tetrandrine suppresses lipopolysaccharide-induced microglial activation by inhibiting NF-kappaB pathway. Acta Pharmacol Sin. 2008;29:245-51 pubmed publisher
    ..Our results suggest that TET might modulate LPS-induced microglial activation by inhibiting the NF-kappaB-mediated release of inflammatory factors. ..
  20. Fernandes M, Custódio J, Santos M, Moreno A, Vicente J. Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress. Mitochondrion. 2006;6:176-85 pubmed
    ..The direct immediate protective role of tetrandrine against mitochondrial oxidative stress may be relevant to clarify the mechanisms responsible for its multiple pharmacological actions. ..
  21. Li R, Xie L, Zhu Z, Liu Q, Hu Y, Jiang X, et al. Reversion of pH-induced physiological drug resistance: a novel function of copolymeric nanoparticles. PLoS ONE. 2011;6:e24172 pubmed publisher
    ..This study emphasized the importance of cancer microenvironmental factors in anticancer drug resistance and revealed the superiority of nanoscale drug carrier from a different aspect. ..
  22. Dai C, Xiong H, Tang L, Zhang X, Liang Y, Zeng M, et al. Tetrandrine achieved plasma concentrations capable of reversing MDR in vitro and had no apparent effect on doxorubicin pharmacokinetics in mice. Cancer Chemother Pharmacol. 2007;60:741-50 pubmed
  23. He F, Qiu B, Li T, Xie Q, Cui D, Huang X, et al. Tetrandrine suppresses amyloid-?-induced inflammatory cytokines by inhibiting NF-?B pathway in murine BV2 microglial cells. Int Immunopharmacol. 2011;11:1220-5 pubmed publisher
    ..In conclusion, tetrandrine can decrease microglial detriment of neurotoxicity while maintaining microglial benefit of neuroprotection. Tetrandrine may be an efficacious and promising remedy in the treatment of AD. ..
  24. Wu C, Wang Y, Lin C, Chen H, Chen Y. Tetrandrine down-regulates ERK/NF-?B signaling and inhibits activation of mesangial cells. Toxicol In Vitro. 2011;25:1834-40 pubmed publisher
    ..TET down-regulated ERK/NF-?B signaling and inhibited the expression of inflammatory mediators NO and MMP-9. Since these mediators appear to activate mesangial cells, TET may play an important role in prevention of glomerulonephritis. ..
  25. Takahashi Makise N, Suzu S, Hiyoshi M, Ohsugi T, Katano H, Umezawa K, et al. Biscoclaurine alkaloid cepharanthine inhibits the growth of primary effusion lymphoma in vitro and in vivo and induces apoptosis via suppression of the NF-kappaB pathway. Int J Cancer. 2009;125:1464-72 pubmed publisher
    ..These results indicate that NF-kappaB could be an ideal molecular target for treating PEL and that CEP is quite useful as a unique therapeutic agent for PEL. ..
  26. Chen B, Cheng J, Shen M, Gao F, Xu W, Shen H, et al. Magnetic nanoparticle of Fe3O4 and 5-bromotetrandrin interact synergistically to induce apoptosis by daunorubicin in leukemia cells. Int J Nanomedicine. 2009;4:65-71 pubmed
    ..Thus our in vitro data strongly suggests a potential clinical application of MNP(Fe(3)O(4)) and BrTet combination on CML. ..
  27. Chen Y, Chen J, Tseng S. Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats. Int J Cancer. 2009;124:2260-9 pubmed publisher
    ..Tetrandrine has potential as a treatment for gliomas. ..
  28. Chen L, Chen L, Lv Y, Cui Z, Bei G, Qin G, et al. Tetrandrine ameliorates cognitive impairment via inhibiting astrocyte-derived S100B activation in a rat model of chronic cerebral hypoperfusion. Neurol Res. 2013;35:614-21 pubmed publisher
  29. Hsu Y, Chiu Y, Cheng C, Wu C, Lin Y, Huang Y. Antifibrotic effects of tetrandrine on hepatic stellate cells and rats with liver fibrosis. J Gastroenterol Hepatol. 2007;22:99-111 pubmed
    ..Tetrandrine exerts antifibrotic effects in both HSC-T6 cells and in rats with DMN-induced fibrosis. ..
  30. Yan C, Xin Ming Q, Li Kun G, Lin Lin L, Fang Ping C, Ying X, et al. Tetrandrine-induced apoptosis in rat primary hepatocytes is initiated from mitochondria: caspases and endonuclease G (Endo G) pathway. Toxicology. 2006;218:1-12 pubmed
    ..In addition, a caspase-independent pathway indicated by Endo G also contributed to apoptosis caused by tetrandrine. Meanwhile, ROS was proved an important inducer in this apoptosis process. ..
  31. Li R, Li X, Xie L, Ding D, Hu Y, Qian X, et al. Preparation and evaluation of PEG-PCL nanoparticles for local tetradrine delivery. Int J Pharm. 2009;379:158-66 pubmed publisher
    ..Nanoparticles prepared from the di-block copolymer with a particle size around 300nm and the hydrophobic composition about 80% was determined as the most effective drug carrier for further studies. ..
  32. Xiaoyan A, Jun Y, Min W, Haiyue Z, Li C, Kangde Y, et al. Preparation of chitosan-gelatin scaffold containing tetrandrine-loaded nano-aggregates and its controlled release behavior. Int J Pharm. 2008;350:257-64 pubmed
    ..Here a room can be provided for the scaffolds to sustained release bioactive component in tissue engineering. ..
  33. Li X, Zhen D, Lu X, Xu H, Shao Y, Xue Q, et al. Enhanced cytotoxicity and activation of ROS-dependent c-Jun NH2-terminal kinase and caspase-3 by low doses of tetrandrine-loaded nanoparticles in Lovo cells--a possible Trojan strategy against cancer. Eur J Pharm Biopharm. 2010;75:334-40 pubmed publisher
    ..Although the present results suggested that Tet-np could be a potential useful chemotherapeutic tool, intensive researches are still warranted. ..
  34. Huang P, Xu Y, Wei R, Li H, Tang Y, Liu J, et al. Efficacy of tetrandrine on lowering intraocular pressure in animal model with ocular hypertension. J Glaucoma. 2011;20:183-8 pubmed publisher
    ..This study provides evidence that tetrandrine has a major effect on lowering IOP levels in the ocular hypertension rat model. The functional mechanisms of tetrandrine require further investigation. ..
  35. Furusawa S, Wu J. The effects of biscoclaurine alkaloid cepharanthine on mammalian cells: implications for cancer, shock, and inflammatory diseases. Life Sci. 2007;80:1073-9 pubmed
    ..The purpose of our review is to describe various therapeutic approaches using cepharanthine and their potential efficacy. ..
  36. Liscombe D, Macleod B, Loukanina N, Nandi O, Facchini P. Evidence for the monophyletic evolution of benzylisoquinoline alkaloid biosynthesis in angiosperms. Phytochemistry. 2005;66:2501-20 pubmed also reported. Pathogenesis--related (PR)10 and Bet v 1 major allergen proteins share homology with NCS, but recombinant polypeptides were devoid of NCS activity...
  37. Chen B, Du J, Zhang C, Cheng J, Gao F, Lu Z. [Using protein chips to study mechanism underlying reversion of drug resistance in leukemia cells in tetrandrine alone or in combination with droloxifene]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005;13:999-1003 pubmed
    ..05). The expression of MRP1 and BCRP are not closely correlated with the reversal mechanism of Tet and Drol, and which may be involved in the mechanism of this combination to reverse multidrug resistance in leukemia...
  38. Hsu Y, Chiu Y, Lee C, Wu C, Huang Y. Anti-fibrotic effects of tetrandrine on bile-duct ligated rats. Can J Physiol Pharmacol. 2006;84:967-76 pubmed
  39. Wei Y, Xu L, Liang Y, Xu X, Zhao X. Berbamine exhibits potent antitumor effects on imatinib-resistant CML cells in vitro and in vivo. Acta Pharmacol Sin. 2009;30:451-7 pubmed publisher
    ..Berbamine in combination with imatinib restored the chemo-sensitivity of K562-r cells to imatinib. Our findings suggest that berbamine may be useful in treating imatinib-resistant CML patients. ..
  40. Chen B, Yin L, Cheng J, Ding J, Gao C, Sun Y, et al. Effect of D, L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol and tetrandrine on the reversion of multidrug resistance in K562/A02 cells. Hematology. 2011;16:24-30 pubmed publisher
    ..Moreover, a positive correlation was observed between GCS and P-gp. Thus, our results suggest that a potential clinical application of PDMP in combination with Tet may enhance chemosensitivity in leukemia. ..
  41. Marinho A, Barbosa Filho J, Oliveira E. A validated method for the simultaneous quantitation of bioactive alkaloid markers in the leaf ethanolic extract of Cissampelos sympodialis Eichl.: a phenological variation study. Phytochem Anal. 2012;23:426-32 pubmed publisher
    ..Several alkaloids have been identified in the extract, including warifteine and methylwarifteine (bisbenzylisoquinoline), as well as milonine (morphinandienone)...
  42. Wan J, Liu T, Mei L, Li J, Gong K, Yu C, et al. Synergistic antitumour activity of sorafenib in combination with tetrandrine is mediated by reactive oxygen species (ROS)/Akt signaling. Br J Cancer. 2013;109:342-50 pubmed publisher
    ..This finding provides a novel approach that may broaden the clinical application of sorafenib. ..
  43. Tamatani T, Azuma M, Motegi K, Takamaru N, Kawashima Y, Bando T. Cepharanthin-enhanced radiosensitivity through the inhibition of radiation-induced nuclear factor-kappaB activity in human oral squamous cell carcinoma cells. Int J Oncol. 2007;31:761-8 pubmed
    ..These findings suggested that the combination of radiotherapy and cepharanthin could enhance radiosensitivity in the treatment of human oral cancer. ..
  44. Han X, Lamshöft M, Grobe N, Ren X, Fist A, Kutchan T, et al. The biosynthesis of papaverine proceeds via (S)-reticuline. Phytochemistry. 2010;71:1305-12 pubmed publisher
    ..The final step to papaverine is dehydrogenation of the 1,2-bond, yielding the target compound papaverine. We conclusively show herein that the previously claimed norreticuline does not play a role in the biosynthesis of papaverine...
  45. Liu C, Gong K, Mao X, Li W. Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma. Int J Cancer. 2011;129:1519-31 pubmed publisher
    ..Moreover, the results of xenograft in nude mice were consistent with that of the in vitro studies. Therefore, our data suggest that tetrandrine may be a promising agent for the treatment of HCC as a regulator of ROS/Akt pathway. ..
  46. Lin S, Li S, Chen Z, He X, Zhang Y, Xu X, et al. Formation, recognition and bioactivities of a novel G-quadruplex in the STAT3 gene. Bioorg Med Chem Lett. 2011;21:5987-91 pubmed publisher
    ..Our results provide a new clue for studying the G-quadruplex formation, recognition and function in the 3'-flanking region of gene. ..
  47. Wei N, Liu G, Chen X, Liu Q, Wang F, Sun H. H1, a derivative of Tetrandrine, exerts anti-MDR activity by initiating intrinsic apoptosis pathway and inhibiting the activation of Erk1/2 and Akt1/2. Biochem Pharmacol. 2011;82:1593-603 pubmed publisher
    ..These findings further support the potential of H1 to be used in clinical trial of MDR cancer treatment. ..
  48. Li S, Ji Z, Zou M, Nie X, Shi Y, Cheng G. Preparation, characterization, pharmacokinetics and tissue distribution of solid lipid nanoparticles loaded with tetrandrine. AAPS PharmSciTech. 2011;12:1011-8 pubmed publisher
    ..In conclusion, TET-SLNs with a small particle size, and high EE, can be produced by the method described in this study. The SLN system is a promising approach for the intravenous delivery of tetrandrine. ..
  49. Harada K, Ferdous T, Itashiki Y, Takii M, Mano T, Mori Y, et al. Cepharanthine inhibits angiogenesis and tumorigenicity of human oral squamous cell carcinoma cells by suppressing expression of vascular endothelial growth factor and interleukin-8. Int J Oncol. 2009;35:1025-35 pubmed
    ..These findings suggest that Cepharanthine can suppress angiogenesis and growth of OSCC cells by inhibiting expression of VEGF and IL-8 involved in the blockade of NF-kappaB activity. ..
  50. Chen B, Cheng J, Wu Y, Gao F, Xu W, Shen H, et al. Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5-bromotetrandrine in xenograft nude-mice. Int J Nanomedicine. 2009;4:73-8 pubmed
    ..It is concluded that 5-BrTet and MNP-Fe(3)O(4) combined with DNR had a significant tumor-suppressing effect on a MDR leukemia cells xenograft model. ..
  51. Li X, Su B, Liu R, Wu D, He D. Tetrandrine induces apoptosis and triggers caspase cascade in human bladder cancer cells. J Surg Res. 2011;166:e45-51 pubmed publisher
    ..Our results suggest that tetrandrine merits further in vivo investigation as a novel bladder cancer chemopreventive and chemotherapeutic agent in the clinical setting. ..
  52. Wang J, Chen B, Cheng J, Xu W, Sun X. [Comparison of reversal effects of 5-bromotetrandrine and tetrandrine on P-glycoprotein-dependent Resistance to adriamycin in human lukemia cell line K562/A02]. Ai Zheng. 2008;27:491-5 pubmed
    ..0 micromol/L Tet(P<0.05). BrTet could reverse MDR in vitro. Its activity may be related to the inhibition of P-gp overexpression and the increase in intracellular accumulation of anticancer drugs. ..
  53. Wang J, Chen B, Cheng J, Cai X, Xia G, Liu R, et al. Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin. Int J Nanomedicine. 2011;6:1027-34 pubmed publisher