https://scholars.lib.ntu.edu.tw/handle/123456789/435139
標題: | Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells | 作者: | SHIOU-HWA JEE Shen S.-C. Tseng C.-R. HSIEN-CHING CHIU Kuo M.-L. |
公開日期: | 1998 | 出版社: | Blackwell Publishing Inc. | 卷: | 111 | 期: | 4 | 起(迄)頁: | 656-661 | 來源出版物: | Journal of Investigative Dermatology | 摘要: | Curcumin, a potent antioxidant and chemopreventive agent, has recently been found to be capable of inducing apoptosis in human hepatoma and leukemia cells by way of an elusive mechanism. Here, we demonstrate that curcumin also induces apoptosis in human basal cell carcinoma cells in a dose- and time- dependent manner, as evidenced by internucleosomal DNA fragmentation and morphologic change. In our study, consistent with the occurrence of DNA fragmentation, nuclear p53 protein initially increased at 12 h and peaked at 48 h after curcumin treatment. Prior treatment of cells with cycloheximide or actinomycin D abolished the p53 increase and apoptosis induced by curcumin, suggesting that either de novo p53 protein synthesis or some proteins synthesis for stabilization of p53 is required for apoptosis. In electrophoretic mobility gel-shift assays, nuclear extracts of cells treated with curcumin displayed distinct patterns of binding between p53 and its consensus binding site. Supportive of these findings, p53 downstream targets, including p21(CIP1/WAF1) and Gadd45, could be induced to localize on the nucleus by curcumin with similar p53 kinetics. Moreover, we immunoprecipitated extracts from basal cell carcinoma cells with different anti-p53 antibodies, which are known to be specific for wild-type or mutant p53 protein. The results reveal that basal cell carcinoma cells contain exclusively wild-type p53; however, curcumin treatment did not interfere with cell cycling. Similarly, the apoptosis suppressor Bcl-2 and promoter Bax were not changed with the curcumin treatment. Finally, treatment of cells with p53 antisense oligonucleotide could effectively prevent curcumin-induced intracellular p53 protein increase and apoptosis, but sense p53 oligonucleotide could not. Thus, our data suggest that the p53-associated signaling pathway is critically involved in curcumin-mediated apoptotic cell death. This evidence also suggests that curcumin may be a potent agent for skin cancer prevention or therapy. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0031716184&doi=10.1046%2fj.1523-1747.1998.00352.x&partnerID=40&md5=9bfde6e87930285753b4fffc0d1b0d3d https://scholars.lib.ntu.edu.tw/handle/123456789/435139 |
ISSN: | 0022-202X | DOI: | 10.1046/j.1523-1747.1998.00352.x | SDG/關鍵字: | curcumin; cycloheximide; dactinomycin; DNA fragment; protein Bax; protein bcl 2; protein p53; apoptosis; article; basal cell carcinoma; cancer cell; cell cycle; DNA damage; dose time effect relation; gel mobility shift assay; human; human cell; pathogenesis; priority journal; protein binding; signal transduction |
顯示於: | 醫學系 |
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