CEPHARANTHINE INHIBITS PROLIFERATION OF CANCER-CELLS BY INDUCING APOPTOSIS

Cepharanthine, a biscoclaurine alkaloid extracted from Stephania cepha rantha Hayata, was examined for a possible apoptosis-inducing effect i n 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 mu g/ml) markedly induced apoptosis in resista nt cells after 6 h and 24 h. By the means of agarose electrophoresis t he DNA ladder was detected in cell lines treated with cepharanthine fo r 24 h. Cepharanthine (1-10 mu g/ml) also induced the production of re active oxygen species in P388/DOX cells, while no such cepharanthine-i nduced increase in reactive oxygen species was observed in P388/S cell s. Flow cytometry analysis showed a high level of Fas-antigen expressi on in P388/DOX cells treated with cepharanthine. Furthermore, we found that the inhibition of DNA and protein synthesis caused by cepharanth ine (10 mu g/ml) was more significant in resistant cells than in sensi tive cells. Cepharanthine had no effect on the GSH content of P388/S a nd 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 th e production of reactive oxygen species and Fas-antigen expression in tumor cells. (C) 1998 Prous Science. All rights reserved.