Icaritin Exerts Anti-Cancer Effects through Modulating Pyroptosis and Immune Activities in Hepatocellular Carcinoma

Author:

Jiao Yuanyuan12,Li Wenqian23,Yang Wen2,Wang Mingyu2,Xing Yaling2,Wang Shengqi12

Affiliation:

1. College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Poyanghu Road, Jinghai District, Tianjin 301617, China

2. Bioinformatics Center of AMMS, Taiping Road, Haidian District, Beijing 100850, China

3. College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Daxue Road, Jinan 250355, China

Abstract

Icaritin (ICT), a natural compound extracted from the dried leaves of the genus Epimedium, possesses antitumor and immunomodulatory properties. However, the mechanisms through which ICT modulates pyroptosis and immune response in hepatocellular carcinoma (HCC) remain unclear. This study demonstrated that ICT exhibits pyroptosis-inducing and anti-hepatocarcinoma effects. Specifically, the caspase1-GSDMD and caspase3-GSDME pathways were found to be involved in ICT-triggered pyroptosis. Furthermore, ICT promoted pyroptosis in co-cultivation of HepG2 cells and macrophages, regulating the release of inflammatory cytokines and the transformation of macrophages into a proinflammatory phenotype. In the Hepa1-6+Luc liver cancer model, ICT treatment significantly increased the expression of cleaved-caspase1, cleaved-caspase3, and granzyme B, modulated cytokine secretion, and stimulated CD8+ T cell infiltration, resulting in a reduction in tumor growth. In conclusion, the findings in this research suggested that ICT may modulate cell pyroptosis in HCC and subsequently regulate the immune microenvironment of the tumor. These observations may expand the understanding of the pharmacological mechanism of ICT, as well as the therapy of liver cancer.

Funder

National Natural Science Foundation of China

Publisher

MDPI AG

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