| Summary: | 碩士 === 高雄醫學大學 === 天然藥物研究所 === 99 === Natural compounds from plants have been an important source for the discovery of anticancer drugs. It is known that withanolides, a group of steroidal lactones found in Solanaceae plants, exhibit anti-tumor, anti-angiogenic, anti-invasive, and chemo-preventive activities. In a previous study, we have demonstrated that a withanolide, tubocapsenolide A (TA), induced cycle arrest and apoptosis in human breast cancer MDA-MB-231 cells which was associated with the inhibition of heat shock protein 90 (hsp90). In order to confirm whether hsp90 inhibition is a general property of withanolides and to analyze the structure-activity of relationship, nine withanolide compounds were tested for their inhibitory effects on heat shock proteins and cell viability. Our results showed that most of the withanolides inhibited hsp90 function, as evident by degradation of hsp90 client proteins and induction of hsp70. The inhibitory effects of withanolides on hsp90 chaperone activity were further confirmed using in vivo heat shock luciferase activity recovery assays. Importantly, hsp 90 inhibition by withanolides correlated with their ability to induce cell death. Therefore, withanolides can be considered as a new type of inhibitor of hsp90, which has the potential to be developed as a novel strategy for cancer treatment.
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