Lyu Qing, Tou Fangfang, Su Hong, Wu Xiaoyong, Chen Xinyi, Zheng Zhi
School of Life Sciences, Tsinghua University, Beijing, 100084, PR China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China.
Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029, PR China.
Biochem Biophys Res Commun. 2015 Jun 19;462(1):38-45. doi: 10.1016/j.bbrc.2015.04.102. Epub 2015 Apr 29.
Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death.
自噬在真核细胞中具有进化保守性，它吞噬细胞内的长寿蛋白和细胞器，并通过与溶酶体融合来降解其内容物，借此细胞获得用于合成新分子的回收构建模块。在本研究中，我们揭示了浙贝母碱可诱导结肠癌细胞系HCT - 116细胞死亡并增强自噬流。我们确定浙贝母碱通过抑制上游信号来抑制mTOR的磷酸化，从而增强自噬流。敲低ATG5可显著降低浙贝母碱诱导的野生型HCT - 116细胞死亡，而用浙贝母碱处理Bax/Bak缺陷型细胞则导致显著的细胞死亡。总之，我们的发现表明浙贝母碱通过诱导自噬性细胞死亡来抑制结肠癌细胞的增殖和生长。
