Taniguchi T, Iizumi Y, Watanabe M, Masuda M, Morita M, Aono Y, Toriyama S, Oishi M, Goi W, Sakai T
Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Cell Death Dis. 2016 May 5;7(5):e2211. doi: 10.1038/cddis.2016.114.
Resveratrol has various attractive bioactivities, such as prevention of cancer, neurodegenerative disorders, and obesity-related diseases. Therefore, identifying its direct binding proteins is expected to discover druggable targets. Sirtuin 1 and phosphodiesterases have so far been found as the direct molecular targets of resveratrol. We herein identified 11 novel resveratrol-binding proteins, including the DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5, also known as p68), using resveratrol-immobilized beads. Treatment with resveratrol induced degradation of DDX5 in prostate cancer cells. Depletion of DDX5 caused apoptosis by inhibiting mammalian target of rapamycin complex 1 (mTORC1) signaling. Moreover, knockdown of DDX5 attenuated the inhibitory activities of resveratrol against mTORC1 signaling and cancer cell growth. These data show that resveratrol directly targets DDX5 and induces cancer cell death by inhibiting the mTORC1 pathway.
白藜芦醇具有多种引人关注的生物活性，如预防癌症、神经退行性疾病和肥胖相关疾病。因此，鉴定其直接结合蛋白有望发现可成药靶点。到目前为止，已发现沉默调节蛋白1和磷酸二酯酶是白藜芦醇的直接分子靶点。我们在此使用固定有白藜芦醇的珠子鉴定出11种新的白藜芦醇结合蛋白，包括DEAD（天冬氨酸-谷氨酸-丙氨酸-天冬氨酸）盒解旋酶5（DDX5，也称为p68）。白藜芦醇处理可诱导前列腺癌细胞中DDX5的降解。DDX5的缺失通过抑制雷帕霉素复合物1（mTORC1）信号通路导致细胞凋亡。此外，敲低DDX5可减弱白藜芦醇对mTORC1信号通路和癌细胞生长的抑制活性。这些数据表明，白藜芦醇直接靶向DDX5并通过抑制mTORC1途径诱导癌细胞死亡。
