自噬
粒体自噬
溶酶体
化学
自噬体
癌细胞
细胞生物学
癌症研究
细胞凋亡
程序性细胞死亡
癌症
生物
生物化学
遗传学
酶
作者
Shuting Yang,Jinbao Fan,Tingting Liu,Shuai Ning,Jiahao Xu,Yingjun Zhou,Xu Deng
标识
DOI:10.1021/acs.jmedchem.2c00275
摘要
Inhibition of autophagy has been widely viewed as a promising strategy for anticancer therapy. However, few effective and specific autophagy inhibitors have been reported. Herein, we described the design, synthesis, and biological characteristics of new analogues of strigolactones (SLs), an emerging class of plant hormones, against colorectal cancers. Among them, an enantiopure analogue 6 exerted potent and selective cytotoxicity against colorectal cancer cells, but not normal human colon mucosal epithelial cells, which were further confirmed by the plate colony formation assay. Moreover, it significantly inhibited tumor growth in an HCT116 xenograft mouse model with low toxicity. Mechanistically, it is associated with selective induction of cell apoptosis and cell cycle arrest. Remarkably, 6 acted as a potent autophagy/mitophagy inhibitor by selectively increasing the autophagic flux while blocking the autophagosome–lysosome fusion in HCT116 cells. This study features stereo-defined SLs as novel autophagy inhibitors with high cancer cell specificity, which paves a new path for anticolorectal cancer therapy.
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