Apoptin induces pyroptosis of colorectal cancer cells via the GSDME-dependent pathway

文献类型： 外文期刊

第一作者： Liu, Zirui

作者： Liu, Zirui;Jin, Ningyi;Liu, Zirui;Li, Nan;Li, Wenjie;Shang, Chao;Song, Gaojie;Li, Shanzhi;Cong, Jianan;Li, Tingyu;Xiu, Zhiru;Lu, Jing;Ge, Chenchen;Yang, Xia;Li, Yaru;Sun, Lili;Li, Xiao;Jin, Ningyi;Li, Yiquan;Zhu, Yilong;Li, Xiao;Jin, Ningyi;Li, Xiao;Jin, Ningyi;Sun, Lili

作者机构：

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES （ 影响因子：10.75； 五年影响因子：9.445 ）

ISSN： 1449-2288

年卷期： 2022 年 18 卷 2 期

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收录情况： SCI

摘要： Apoptin is a small molecular weight protein encoded by the VP3 gene of chicken anemia virus (CAV). It can induce apoptosis of tumor cells and play anti-tumorigenic functions. In this study, we identified a time-dependent inhibitory role of apoptin on the viability of HCT116 cells. We also demonstrated that apoptin induces pyroptosis through cleaved caspase 3, and with a concomitant cleavage of gasdermin E (GSDME) rather than GSDMD. GSDME knockdown switched the apoptin-induced cell death from pyroptosis to apoptosis in vitro. Furthermore, we demonstrated that the effect of apoptin on GSDME-dependent pyroptosis could be mitigated by caspase-3 and caspase-9 siRNA knockdown. Additionally, apoptin enhanced the intracellular reactive oxygen species (ROS), causing aggregation of the mitochondrial membrane protein Tom20. Moreover, bax and cytochrome c were released to the activating caspase-9, eventually triggering pyroptosis. Therefore, GSDME mediates the apoptin-induced pyroptosis through the mitochondrial apoptotic pathway. Finally, using nude mice xenografted with HCT116 cells, we found that apoptin induces pyroptosis and significantly inhibits tumor growth. Based on this mechanism, apoptin may provide a new strategy for colorectal cancer therapy.

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