2. Academic Validation
  3. Apoptin induces pyroptosis of colorectal cancer cells via the GSDME-dependent pathway

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

  • Int J Biol Sci. 2022 Jan 1;18(2):717-730. doi: 10.7150/ijbs.64350.
Zirui Liu 1 2,  Yiquan Li 3,  Yilong Zhu 3,  Nan Li 2,  Wenjie Li 2,  Chao Shang 2,  Gaojie Song 2,  Shanzhi Li 2,  Jianan Cong 2,  Tingyu Li 2,  Zhiru Xiu 2,  Jing Lu 2,  Chenchen Ge 2,  Xia Yang 2,  Yaru Li 2,  Lili Sun 2 4,  Xiao Li 2 3 5,  Ningyi Jin 1 2 3 5
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
  • 2 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 130122, China.
  • 3 Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, 130021, China.
  • 4 Department of Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun, 130012, China.
  • 5 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China.
PMID: 35002520 DOI: 10.7150/ijbs.64350
Abstract

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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