p53-independent pRB degradation contributes to a drug-induced apoptosis in AGS cells.
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.
Jin
Yan
Y
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Leung
Wai Keung
WK
Sung
Joseph Jao-Yiu
JJ
Wu
Jia Rui
JR
D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D045744:Cell Line, Tumor; D020552:Comet Assay; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004249:DNA Damage; D053938:DNA Fragmentation; D004224:Diterpenes / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D005799:Genes, Dominant; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism / Q000502:physiology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*
D015853:Cysteine Proteinase Inhibitors; D004224:Diterpenes; D004791:Enzyme Inhibitors; D010616:Phenanthrenes; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C068051:tripchlorolide; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex