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 approximately 20 microg/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 G1 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-1beta 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 G1 arrest via expression of p21(WAF1) and apoptosis through caspase 3.
Harada
K
K
Second Department of Oral and Maxillofacial Surgery, University of Tokushima, School of Dentistry, 3-18-15 Kuramoto, Tokushima 770-8504, Japan. harako@dent.tokushima-u.ac.jp
Bando
T
T
Yoshida
H
H
Sato
M
M
D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis; D044182:Benzylisoquinolines; D015153:Blotting, Western; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy*; D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology; D053938:DNA Fragmentation; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D014407:Tumor Cells, Cultured / Q000187:drug effects; D052117:Benzodioxoles
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D053148:Caspase 3; D020169:Caspases; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; C006947:cepharanthine; D052117:Benzodioxoles; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse