Sterigmatocystin induces autophagic and apoptotic cell death of liver cancer cells via downregulation of XIAP

Xu Chen; Zhengping Che; Jiajia Wu; Cheng Zeng; Xiao-Long Yang; Lin Zhang; Zhenghong Lin

doi:10.1016/j.heliyon.2024.e29567

Sterigmatocystin induces autophagic and apoptotic cell death of liver cancer cells via downregulation of XIAP

Heliyon. 2024 Apr 16;10(8):e29567. doi: 10.1016/j.heliyon.2024.e29567. eCollection 2024 Apr 30.

Authors

Xu Chen^{1

2}, Zhengping Che², Jiajia Wu², Cheng Zeng², Xiao-Long Yang³, Lin Zhang¹, Zhenghong Lin^{1

2}

Affiliations

¹ Chongqing University Jiangjin Hospital, Chongqing, 402260, PR China.
² School of Life Sciences, Chongqing University, Chongqing, 401331, PR China.
³ The School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, 430074, PR China.

Abstract

XIAP, or the X-linked Inhibitor of Apoptosis Protein, is the most extensively studied member within the IAP gene family. It possesses the capability to impede apoptosis through direct inhibition of caspase activity. Various kinds of cancers overexpress XIAP to enable cancer cells to avoid apoptosis. Consequently, the inhibition of XIAP holds significant clinical implications for the development of anti-tumor medications and the treatment of cancer. In this study, sterigmatocystin, a natural compound obtained from the genus asperigillus, was demonstrated to be able to induce apoptotic and autophagic cell death in liver cancer cells. Mechanistically, sterigmatocystin induces apoptosis by downregulation of XIAP expression. Additionally, sterigmatocystin treatment induces cell cycle arrest, blocks cell proliferation, and slows down colony formation in liver cancer cells. Importantly, sterigmatocystin exhibits a remarkable therapeutic effect in a nude mice model. Our findings revealed a novel mechanism through which sterigmatocystin induces apoptotic and autophagic cell death of liver cancer cells by suppressing XIAP expression, this offers a promising therapeutic approach for treating liver cancer patients.

Keywords: Apoptosis; Autophagy; Liver cancer; Sterigmatocystin; XIAP.