- 著者
- Eun-Sun Choi Taeho Chung Jun-Sung Kim Hakmo Lee Ki Han Kwon Nam-Pyo Cho Sung-Dae Cho
- 出版者
- 日本酸化ストレス学会
- 雑誌
- Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)
- 巻号頁・発行日
- vol.53, no.2, pp.89-93, 2013 (Released:2013-08-31)
- 参考文献数
- 40
- 被引用文献数
- 3 12
Mithramycin A (Mith) is an aureolic acid-type polyketide produced by various soil bacteria of the genus Streptomyces. Mith inhibits myeloid cell leukemia-1 (Mcl-1) to induce apoptosis in prostate cancer, but the molecular mechanism underlying this process has not been fully elucidated. The aim of this study was therefore to investigate the detailed molecular mechanism related to Mith-induced apoptosis in prostate cancer cells. Mith decreased the phosphorylation of mammalian target of rapamycin (mTOR) in both cell lines overexpressing phospho-mTOR compared to RWPE-1 human normal prostate epithelial cells. Mith significantly induced truncated Bid (tBid) and siRNA-mediated knock-down of Mcl-1 increased tBid protein levels. Moreover, Mith also inhibited the phosphorylation of mTOR on serine 2448 and Mcl-1, and increased tBid protein in prostate tumors in athymic nude mice bearing DU145 cells as xenografts. Thus, Mith acts as an effective tumor growth inhibitor in prostate cancer cells through the mTOR/Mcl-1/tBid signaling pathway.