Cepharanthine inhibits proliferation of cancer cells by inducing apoptosis.
Cepharanthine, a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata was examined for a possible apoptosis-inducing effect in murine P388 doxorubicin-sensitive (P388/S) and -resistant (P388/DOX) cells. A significant increase in LDH release from cells was observed after P388/S and P388/DOX cells had been exposed to cepharanthine for 24 h. Cepharanthine (10 micrograms/ml) markedly induced apoptosis in resistant cells after 6 h and 24 h. By the means of agarose electrophoresis the DNA ladder was detected in cell lines treated with cepharanthine for 24 h. Cepharanthine (1-10 micrograms/ml) also induced the production of reactive oxygen species in P388/DOX cells, while no such cepharanthine-induced increase in reactive oxygen species was observed in P388/S cells. Flow cytometry analysis showed a high level of Fas-antigen expression in P388/DOX cells treated with cepharanthine. Furthermore, we found that the inhibitition of DNA and protein synthesis caused by cepharanthine (10 micrograms/ml) was more significant in resistant cells than in sensitive cells. Cepharanthine had no effect on the GSH content of P388/S and P388/DOX cells. Our experimental results suggest that cepharanthin can induce apoptosis both in P388/S and P388/DOX cells, especially in the latter. Apoptosis induced by cepharanthine may be implicated in the production of reactive oxygen species and Fas-antigen expression in tumor cells.
Furusawa
S
S
Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku College of Pharmacy, Sendai, Japan.
Wu
J
J
Fujimura
T
T
Nakano
S
S
Nemoto
S
S
Takayanagi
M
M
Sasaki
K
K
Takayanagi
Y
Y
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007941:Leukemia P388 / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D017382:Reactive Oxygen Species; D014407:Tumor Cells, Cultured; D052117:Benzodioxoles
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D017382:Reactive Oxygen Species; C006947:cepharanthine; D052117:Benzodioxoles