Characteristics of antitumour activity of cepharanthin against a human adenosquamous cell carcinoma cell line

Cepharanthin is one of the biscoclaurine alkaloids widely used for treatment of many acute and chronic diseases; snakebite, bronchial asthma, alopecia areata, leukopenia during radiation therapy or anticancer treatment. Recently, it has been reported that cepharanthin exerts antitumour effects by increasing immunological competence of the host or apoptosis-inducing activity. In this study, we examined the antitumour effects of cepharanthin against a human adenosquamous cell carcinoma cell line (TYS). Treatment of TYS cells with cepharanthin (10 similar to 20 mug/ml) resulted in a significant suppression of cell growth. Moreover, it was found by the flow cytometry analysis, nick end labelling or agarose gel electrophoresis, that G I arrest and DNA fragmentation occurred in cepharanthin-treated cells. In addition, it was detected that induction of p21(WAF1) protein and activation of caspase 3 protype, which is one of Interleukin-1 beta converting enzyme (ICE) family proteases, were detected. by Western blotting. The TYS tumour-bearing nude mice were treated with cepharanthin, which was administered subcutaneously (20 mg/kg/day). The cepharanthin treatment results in a significant suppression of tumour growth and an induction of apoptosis. These findings suggest that cepharanthin induces G I arrest via expression of p21(WAF1) and apoptosis through caspase 3. (C) 2001 Elsevier Science Ltd. All rights reserved.