Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18

• DOI: 10.4161/auto.6.8.13336
• Publication Date: 2010-11-04T13:43:37Z
• Authors: Songhai Tian; Jian Lin; Jun Zhou; Xiaolong Wang; Yanjun Li; Xiaobai Ren; Wenyu Yu; Wu Zhong; Junhai Xiao; Fugeng Sheng; Yingyu Chen; Changwen Jin; Song Li; Zhibing Zheng; Bin Xia
• Keywords: 0301 basic medicine; Binding Sites; Indoles; bcl-X Protein; Membrane Proteins; Thiophenes; Models, Biological; 03 medical and health sciences; Autophagy; Humans; Beclin-1; Apoptosis Regulatory Proteins; HeLa Cells

Inhibitors of Bcl-XL/Bcl-2 can induce autophagy by releasing the autophagic protein Beclin 1 from its complexes with these proteins. Here we report a novel compound targeting the BH3 binding groove of Bcl-XL/Bcl-2, Z18, which efficiently induces autophagy-associated cell death in HeLa cells, without apparent apoptosis. Unexpectedly, the inhibition of Beclin 1 and phosphatidylinositol 3-kinase have no obvious effect on Z18-induced autophagy in HeLa cells, implying that it is a non-canonical Beclin 1-independent autophagy. Meanwhile, the accumulation of autophagosomes is positively correlated with Z18-induced cell death and the full flux of autophagy is not necessary.