A Novel Mechanism of Cannabidiol in Suppressing Hepatocellular Carcinoma by Inducing GSDME Dependent Pyroptosis

被引：53
作者：
Shangguan, Fugen [1 ]
Zhou, Hongfei [1 ]
Ma, Nengfang [2 ]
Wu, Shanshan [3 ]
Huang, Huimin [1 ]
Jin, Guihua [1 ]
Wu, Shijia [1 ]
Hong, Weilong [1 ]
Zhuang, Weiwei [1 ]
Xia, Hongping [1 ,4 ]
Lan, Linhua [1 ]
机构：
[1] Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Diag & Treatment Severe Hepatopancreat Di, Wenzhou, Peoples R China
[2] Wenzhou Univ, Sch Life & Environm Sci, Wenzhou, Peoples R China
[3] Wenzhou Med Univ, Affliated Hosp 1, Med Res Ctr, Wenzhou, Peoples R China
[4] Nanjing Med Univ, Natl Hlth Commiss, Key Lab Antibody Tech,Sch Basic Med Sci,Dept Path, State Key Lab Reprod Med,Affiliated Sir Run Run H, Nanjing, Peoples R China
来源：
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2021年 / 9卷
基金：
中国国家自然科学基金;
关键词：
cannabidiol; hepatocellular carcinoma; pyroptosis; integrative stress response; aerobic glycolysis; FACTOR-BINDING PROTEIN-1; GASDERMIN D; INDUCED APOPTOSIS; STRESS-RESPONSE; CELL-DEATH; CANCER; CANNABINOIDS; INHIBITION; CLEAVAGE; PATHWAY;
D O I：
10.3389/fcell.2021.697832
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Cannabidiol (CBD), a phytochemical derived from Cannabis sativa L., has been demonstrated to exhibit promising anti-tumor properties in multiple cancer types. However, the effects of CBD on hepatocellular carcinoma (HCC) cells remain unknown. We have shown that CBD effectively suppresses HCC cell growth in vivo and in vitro, and induced HCC cell pyroptosis in a caspase-3/GSDME-dependent manner. We further demonstrated that accumulation of integrative stress response (ISR) and mitochondrial stress may contribute to the initiation of pyroptotic signaling by CBD. Simultaneously, CBD can repress aerobic glycolysis through modulation of the ATF4-IGFBP1-Akt axis, due to the depletion of ATP and crucial intermediate metabolites. Collectively, these observations indicate that CBD could be considered as a potential compound for HCC therapy.
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页数：16
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