| Summary: | 碩士 === 國立中興大學 === 生物醫學研究所 === 98 === Prodigiosin (PG) has been identified as a new and potential anti-cancer drug in a variety of studies. However, the precise targets of PG-induced apoptosis are still uncovered, and therefore identification of the target is the main focus in this study. By analyzing data from microarray, we found activating transcription factor 3 (ATF3) showed an obvious difference in expression. The results from quantitative real-time RT-PCR analysis and immunoblot analysis on a number of different kinds of cancer cell lines indicated that ATF3 can be highly induced by PG. Further analysis revealed that PG can activate the human ATF3 promoter, and c-Jun N-terminal kinase (JNK) signaling pathway is involved in the up-regulation of ATF3 by PG. Additionally, PG treatment was shown to induce endoplasmic reticulum (ER) stress. Finally, PG-induced apoptosis was significantly reduced by silencing ATF3. Together, these data indicated that PG activates JNK signaling to up-regulates ATF3, which in turn contributes to the induction of apoptosis, partly through ER stress. In conclusion, ATF3 not only plays an important role in PG-induced apoptosis, but also acts a novel molecular taget of PG.
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