Flavopiridol, a cyclin dependent kinase (CDK) inhibitor, induces apoptosis by regulating Bcl-x in oral cancer cells

被引：28

作者：

Mihara, M ^{[1
]}

Shintani, S ^{[1
]}

Nakashiro, K ^{[1
]}

Hamakawa, H ^{[1
]}

机构：

[1] Ehime Univ, Sch Med, Dept Oral & Maxillofacial Surg, Shigenobu, Ehime 7910295, Japan

来源：

ORAL ONCOLOGY | 2003年 / 39卷 / 01期

关键词：

CDK inhibitor; oral cancer; apoptosis;

D O I：

10.1016/S1368-8375(02)00019-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Flavopiridol is a synthetic flavone that inhibits tumor growth by suppressing cyclin-dependent kinases (CDKs). We have investigated effects of flavopiridol in oral squamous cell carcinoma (OSCC). Flavopiridol was found to inhibit the growth of OSCC cells in a time- and dose-dependent manner. Induction of apoptosis was observed in all cells showing accumulated cells with sub-G, DNA contents, DNA fragmentations, and PARP cleavages. While Bcl-2 and Bax expression did not change, Bcl-X-L was down regulated and Bcl-xs was up-regulated after being exposed to flavopiridol. Flavopiridol treatments also resulted in remarkable reductions of cyclin A, cyclin B, and cyclin D1 expressions. We also found that expression levels of CDK activation kinase and CDC25C were reduced, and p34 inactive form CDK2 were up-regulated. Our data indicate that flavopiridol has growth inhibition activities against OSCC. Flavopiridol not only inhibits CDKs directly, but it also inhibits the CDKs activation pathway and activates the Bcl-x apoptotic pathway. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：49 / 55

页数：7

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