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

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 demonstrat...

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Bibliographic Details
Published in:International journal of biological sciences 2022, Vol.18 (2), p.717-730
Main Authors: Liu, Zirui, Li, Yiquan, Zhu, Yilong, 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
Format: Article
Language:English
Subjects:
Adenoviruses
Anemia
Antibodies
Apoptosis
Bax protein
Cancer
Cancer therapies
Caspase-3
Caspase-9
Cell death
Chemotherapy
Colorectal cancer
Colorectal carcinoma
Cytochrome
Cytochrome c
Cytochromes
Cytotoxicity
Flow cytometry
Laboratories
Medical prognosis
Membrane proteins
Membranes
Metastasis
Mitochondria
Molecular weight
Proteins
Pyroptosis
Reactive oxygen species
Research Paper
siRNA
Tumor cells
Tumors
Viruses
VP3 protein
Xenografts
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Summary: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 . 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.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.64350