Cepharanthine exerts antitumor activity on oral squamous cell carcinoma cell lines by induction of p27Kip1.
Cepharanthine is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata. The drug has been widely used for the treatment of many acute and chronic diseases and can exert antitumor effects on several human cancer cells. In this study, we examined the mechanism of the antitumor effects by cepharanthine on a human oral squamous cell carcinoma (SCC) cell line. Treatment of oral SCC cells with cepharanthine (10-20 micrograms/ml) resulted in a significant suppression of cell growth. Cepharanthine preferentially suppressed the growth of B88 cells when compared with other human oral SCC cells. Moreover, it was found, by flow cytometry analysis and Hoechst 33258 staining, that G1 arrest and DNA fragmentation occurred in cepharanthine-treated B88 cells. Furthermore, induction of p27Kip1 and reduction of cyclin E and Skp2 were detected by Western blotting. B88 tumor-bearing nude mice were treated with cepharanthine, which was administered subcutaneously (40 mg/kg/day). The cepharanthine treatment results in a significant suppression of tumor growth. Overall these results indicate that cepharanthine may inhibit the growth of human oral SCC cells by down-regulating cyclin E to induce G1 arrest through a pathway of p27Kip1 induction.
Harada
Koji
K
Second Department of Oral and Maxillofacial Surgery, University of Tokushima, School of Dentistry, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan. harako@dent.tokushima-u.ac.jp
Supriatno
Yamamoto
Shin
S
Kawaguchi
Shin-Ichi
S
Yoshida
Hideo
H
Sato
Mitsunobu
M
D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D044182:Benzylisoquinolines; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D019927:Cyclin E / Q000096:biosynthesis / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D053938:DNA Fragmentation; D004354:Drug Screening Assays, Antitumor; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D052117:Benzodioxoles
D000470:Alkaloids; D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D018797:Cell Cycle Proteins; D019927:Cyclin E; D050760:Cyclin-Dependent Kinase Inhibitor p27; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; C493961:Cdkn1b protein, mouse; C006947:cepharanthine; D052117:Benzodioxoles