Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2 |
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Authors: | Qing-hua Yin Feng-xiang Yan Xu-Yu Zu You-hua Wu Xiao-ping Wu Ming-chu Liao Shu-wen Deng Lei-lan Yin Ying-zhi Zhuang |
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Institution: | (1) Department of Medical Oncology, The First Affiliated Hospital of University of South China, Hengyang, 421001, People’s Republic of China;(2) Institutes of Pharmacy and Pharmacology, University of South China, Hengyang, 421001, People’s Republic of China;(3) Institutes of Clinical Research, The First Affiliated Hospital of University of South China, Hengyang, 421001, People’s Republic of China; |
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Abstract: | Carvacrol is one of the members of monoterpene phenol and is present in the volatile oils of Thymus vulgaris, Carum copticum, origanum and oregano. It is a safe food additive commonly used in our daily life, and few studies have indicated that carvacrol
has anti-hepatocarcinogenic activities. The rationale of the study was to examine whether carvacrol affects apoptosis of human
hepatoma HepG2 cells. In this study, we showed that carvacrol inhibited HepG2 cell growth by inducing apoptosis as evidenced
by Hoechst 33258 stain and Flow cytometric (FCM) analysis. Incubation of HepG2 cells with carvacrol for 24 h induced apoptosis
by the activation of caspase-3, cleavage of PARP and decreased Bcl-2 gene expression. These results demonstrated that a significant
fraction of carvacrol treated cells died by an apoptotic pathway in HepG2 cells. Moreover, carvacrol selectively altered the
phosphorylation state of members of the MAPK superfamily, decreasing phosphorylation of ERK1/2 significantly in a dose-dependent
manner, and activated phosphorylation of p38 but not affecting JNK MAPK phosphorylation. These results suggest that carvacrol
may induce apoptosis by direct activation of the mitochondrial pathway, and the mitogen-activated protein kinase pathway may
play an important role in the antitumor effect of carvacrol. These results have identified, for the first time, the biological
activity of carvacrol in HepG2 cells and should lead to further development of carvacrol for liver disease therapy. |
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Keywords: | Carvacrol Hepatocellular carcinoma Apoptosis Mitochondrial pathway Mitogen-activated protein kinase pathway |
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