Beta-Thujaplicin induces autophagic cell death, apoptosis, and cell cycle arrest through ROS-mediated Akt and p38/ERK MAPK signaling in human hepatocellular carcinoma

β-Thujaplicin treatment increased the reactive oxygen species (ROS) generation, which subsequently led to inhibition of the Akt-mTOR signaling pathway and activation of p38/ERK MAPK signaling pathway. Consequently, (1) increased expression of LAMP1 and LC3B-II, suggesting that β-Thujaplicin increases autophagosome formation. Furthermore, blocking autophagy can effectively alleviate β-Thujaplicin-induced cell death, while inducing autophagy can aggravate cell death, indicating that β-Thujaplicin has a role in ACD. (2) The increase in cleaved PARP1, cleaved caspase-3, and Bax/Bcl-2 ratio caused activation of the mitochondrial-dependent intrinsic apoptotic pathway. (3) Decreased expression of CDK7, Cyclin D1, and Cyclin A2, and increased expression of p21 caused S-phase arrest. Thus, ROS-mediated p38/ERK MAPKs and the Akt-mTOR signaling pathway was shown to be the underlying mechanism of β-Thujaplicin-induced HCC cell death in this study

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β-Thujaplicin induces autophagic cell death, apoptosis, and cell cycle arrest through ROS-mediated Akt and p38/ERK MAPK signaling in human hepatocellular carcinoma. (2019) Guangya Zhang, et al. Cell Death Dis. 2019 Apr;10(4):255. Figure: F6. All organisms Homo sapiens Mus musculus Rattus norvegicus Bos taurus Danio rerio

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