Α-Humulene inhibits hepatocellular carcinoma cell proliferation and induces apoptosis through the inhibition of Akt signaling. (December 2019)

• Record Type: Journal Article
• Authors: Chen, Hao; Yuan, Jingquan; Hao, Ji; Wen, Yanzhang; Lv, Yibing; Chen, Lu; Yang, Xinzhou
• Is Part Of: Food and chemical toxicology. Volume 134(2019)
• Publication Date: 2019-12
• Subjects: α-Humulene -- Hepatocellular carcinoma -- Cytotoxicity -- Apoptosis -- Akt; HCC hepatocellular carcinoma -- Eupatorium odoratum L EO -- HML α-Humulene -- CDDP cisplatin -- FACS fluorescence-activated cell sorting -- Tunel terminal deoxynucleotidyl transferase dUTP nick end labeling -- IHC immunohistochemistry -- Caspase-3 cysteinyl aspartate-specific proteinases 3 -- PARP poly ADP-ribose polymerase -- Akt serine/threonine-specific protein kinase; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2019.110830
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Hepatocellular carcinoma (HCC) is a prevalent malignancy and a leading cause of cancer-related mortality. α-Humulene (HML) is a natural 11-membered monocyclic terpene with three E-configured double bonds isolated from Eupatorium odoratum L. We recently showed that HML has significant anti-HCC activity in vitro and in vivo . We found that HML was cytotoxic to HCC cells and induced mitochondrial apoptosis of HCC cells, promoting caspase-3 activation and PARP cleavage. HCC cells show abnormal Akt signaling to resist apoptosis. Mechanistically, HML was found to inhibit Akt activation, subsequently decreasing GSK-3 and Bad phosphorylation, promoting apoptotic induction. HML also inhibited cell proliferation and enhanced apoptosis in HCC tumor xenografts further highlighting its activity in vivo. Although HML showed minimal cytotoxicity to normal hepatocytes, weight loss was observed in mice administered HML. Taken together, these data provide important and novel insights into the anti-HCC effects of HML through its ability to inhibit Akt, reduced HCC cell proliferation, and enhanced HCC cell apoptotic induction in vitro and in vivo . Graphical abstract: Image 1 Highlights: α-Humulene (HML) inhibits the proliferation of hepatocellular carcinoma (HCC) cells. HML induces HCC cytotoxicity through the induction of intrinsic apoptotic pathways both in vitro and in vivo. Akt inhibition involves in HML-induced apoptosis and anti-proliferation in HCC cells.