Tetrandrine induces apoptosis and growth suppression of colon cancer cells in mice.
Tetrandrine, a bisbenzylisoquinoline alkaloid, exerts antitumor effects against some cancers. We explored tetrandrine's effects on colon cancer with cultured mouse CT-26 cells and with subcutaneous tumors. Tetrandrine induced apoptosis in concentration- and time-dependent manner. Tetrandrine increased expression of ERK 1/2 and p38 MAPK; inhibition of p38 MAPK reduced tetrandrine-induced apoptosis; inhibition of ERK1/2 did not. Tetrandrine had significant effects on tumors including slower growth and longer animal survival time and higher survival rate. Higher dose and earlier treatment were more effective than lower dose and delayed treatment. TUNEL staining showed prominent tetrandrine-induced apoptosis of tumors. 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.
Wu
Jiann-Ming
JM
Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan.
Chen
Yun
Y
Chen
Jin-Cherng
JC
Lin
Tzu-Yu
TY
Tseng
Sheng-Hong
SH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D047368:Tumor Burden; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D047428:Protein Kinase Inhibitors; C009438:tetrandrine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases