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大麻二酚通过诱导GSDME依赖性细胞焦亡抑制肝细胞癌的新机制

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

作者信息

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

机构信息

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

School of Life and Environmental Science, Wenzhou University, Wenzhou, China.

出版信息

Front Cell Dev Biol. 2021 Jul 19;9:697832. doi: 10.3389/fcell.2021.697832. eCollection 2021.

DOI:10.3389/fcell.2021.697832
PMID:34350183
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8327166/
Abstract

Cannabidiol (CBD), a phytochemical derived from 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 and , 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.

摘要

大麻二酚（CBD）是一种从大麻中提取的植物化学物质，已被证明在多种癌症类型中具有良好的抗肿瘤特性。然而，CBD对肝细胞癌（HCC）细胞的影响仍不清楚。我们已经表明，CBD能有效抑制肝癌细胞的生长，并以半胱天冬酶-3/ Gasdermin E依赖的方式诱导肝癌细胞发生焦亡。我们进一步证明，整合应激反应（ISR）和线粒体应激的积累可能有助于CBD引发焦亡信号。同时，由于ATP和关键中间代谢物的消耗，CBD可以通过调节ATF4-IGFBP1-Akt轴来抑制有氧糖酵解。总的来说，这些观察结果表明，CBD可被视为一种潜在的肝癌治疗化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/5d35752c64ff/fcell-09-697832-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/59c587061e81/fcell-09-697832-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/f65488da3b93/fcell-09-697832-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/c8a47bf8fbef/fcell-09-697832-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/948d10aadfa6/fcell-09-697832-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/5d35752c64ff/fcell-09-697832-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/59c587061e81/fcell-09-697832-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/f6db344d754d/fcell-09-697832-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/f65488da3b93/fcell-09-697832-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/f9d95a6b5ae3/fcell-09-697832-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/c8a47bf8fbef/fcell-09-697832-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/948d10aadfa6/fcell-09-697832-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ec1/8327166/5d35752c64ff/fcell-09-697832-g007.jpg

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The Effects of Cannabidiol and Prognostic Role of TRPV2 in Human Endometrial Cancer.
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