AUTHOR=Shangguan Fugen , Zhou Hongfei , Ma Nengfang , Wu Shanshan , Huang Huimin , Jin Guihua , Wu Shijia , Hong Weilong , Zhuang Weiwei , Xia Hongping , Lan Linhua 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.697832

DOI=10.3389/fcell.2021.697832

ISSN=2296-634X

ABSTRACT=<p>Cannabidiol (CBD), a phytochemical derived from <italic>Cannabis sativa</italic> 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 <italic>in vivo</italic> and <italic>in vitro</italic>, 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.</p>