ARTICLE

Cell Research, 15(9):695-703, September 2005

p53-independent pRB degradation contributes to a drug-induced apoptosis in AGS cells

Yan JIN¹, Wai Keung LEUNG², Joseph Jao-Yiu SUNG², Jia Rui WU^1*

¹Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China
²Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

Received, May 23, 2005 Revised, Aug 7, 2005 Accepted, Sep 14, 2005

Correspondence: Jia Rui WU Tel: +86-21-54921128; Fax: +86-21-54921011; E-mail:wujr@sibs.ac.cn

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The retinoblastoma (RB) tumor suppressor protein, pRB, plays an important role in the regulation of mammalian cell cycle. Furthermore, several lines of evidence suggest that pRB also involves in the regulation of apoptosis. In the present study, the degradation of pRB was observed in apoptotic gastric tumor cells treated with a new potent anti-tumor component, tripchlorolide (TC). The inhibition of pRB degradation by a general cysteine protease inhibitor IDAM resulted in the reduction of the apoptotic cells. Furthermore, the survival of the gastric tumor cells under the TC treatment was enhanced by an over-expression of exogenous pRB. These results suggest that the pRB degradation of the gastric tumor cells under the TC treatment involves in the apoptotic progression. In addition, the same extent of TC-induced pRB-degradation was detected in the gastric tumor cells containing a p53 dominant-negative construct, indicating that this kind of pRB degradation is p53-independent.

Keywords: pRB degradation, p53, apoptosis.