Antiproliferative and apoptotic effects of tetrandrine on different human hepatoma cell lines.
Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the dried root of Hang-Fang-Chi (Stephania tetrandra S. Moore), is well known to possess activities including antioxidant, anti-inflammation, anti-fibrotic and anticancer. It is used clinically to treat hypertension and silicosis. In the present study, the anti-proliferative and apoptotic effects of TET were evaluated on three different hepatoma cell lines, namely Hep G2, PLC/PRF/5 and Hep 3B. Using XTT assay, results showed that the IC50 values of TET were 4.35 microM for Hep G2, 9.44 microM for PLC/PRF/5 and 10.41 microM for Hep 3B cells. The CC50 of TET against BNL-CL.2 mouse normal liver cells was 31.12 microM. Interestingly, TET exhibited a lower IC50 value and better selectivity against Hep G2 and PLC/PRF/5 cells than cisplatin. Microscopic observation study, DNA fragmentation assay and flow cytometric analysis further supported apoptotic effect of TET on both PLC/PRF/5 and Hep 3B cells. The cell cycle of PLC/PRF/5 treated with TET appeared to arrest at G2/M phase in a dose-dependent manner, whereas no effect was noted on the cell cycle of Hep 3B cells. The present study concludes that TET exhibited anti-proliferative effect on Hep G2, PLC/PRF/5 and Hep 3B cells in a dose-dependent manner. TET also possesses a lower IC50 and better SI value than cisplatin against Hep G2 and PLC/PRF/5 cells. 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.
Ng
Lean Teik
LT
Department of Biotechnology, Tajen University, Pingtung, Taiwan.
Chiang
Lien-Chai
LC
Lin
Yu-Tseng
YT
Lin
Chun-Ching
CC
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000737:chemistry / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007399:Interphase / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D015394:Molecular Structure
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; C009438:tetrandrine