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Oncol Rep. 2018 Oct;40(4):1985-1993. doi: 10.3892/or.2018.6620. Epub 2018 Aug 2.

Emodin induces apoptosis in human hepatocellular carcinoma HepaRG cells via the mitochondrial caspase‑dependent pathway.

Author information

1
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, P.R. China.
2
School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing 100102.
3
Beijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010.
4
Shanghai Binuo Medical Instrument Co., Ltd., Shanghai 200000, P.R. China.

Abstract

Emodin‑induced hepatotoxicity in vivo and in vitro has been gaining increasing attention. However, the exact molecular pathways underlying these effects remain poorly clarified. The aim of the present study was to evaluate the cytotoxic effect of emodin on HepaRG cells and to define the underlying mechanism. The results demonstrated that emodin evidently inhibited HepaRG cell growth in a dose‑ and time‑dependent manner by blocking cell cycle progression in the S and G2/M phase and by inducing apoptosis. Emodin treatment also resulted in generation of reactive oxygen species (ROS), which abrogated mitochondrial membrane potential (MMP). The above effects were all suppressed by antioxidants, such as N‑acetylcysteine (NAC). Further studies by western blot analysis howed that emodin upregulated p53, p21, Bax, cyclin E, cleaved caspase‑3, 8 and 9, and cleaved poly(ADP‑ribose)polymerase (PARP). However, the protein expression of Bcl‑2, cyclin A and CDK2 was downregulated. Taken together, our results suggest that emodin induces apoptosis via the mitochondrial apoptosis pathway through cell cycle arrest and ROS generation in HepaRG cells.

PMID:
30106438
PMCID:
PMC6111625
DOI:
10.3892/or.2018.6620
[Indexed for MEDLINE]
Free PMC Article

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