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Abstract Title:

Eucalrobusone C suppresses cell proliferation and induces ROS-dependent mitochondrial apoptosis via the p38 MAPK pathway in hepatocellular carcinoma cells.

Abstract Source:

Phytomedicine. 2017 Feb 15 ;25:71-82. Epub 2016 Dec 23. PMID: 28190473

Abstract Author(s):

Kai-Li Jian, Chao Zhang, Zhi-Chun Shang, Lei Yang, Ling-Yi Kong

Article Affiliation:

Kai-Li Jian

Abstract:

BACKGROUND: Eucalyptus extracts have anti-cancer activity against various cancer cells. Formyl-phloroglucinol meroterpenoids (FPMs), which are typical secondary metabolites of the genera Eucalyptus, have many important pharmacological activities.

PURPOSE: Eucalrobusone C (EC), a new bioactive phytochemical, was first isolated from the leaves of Eucalyptus robusta in our laboratory. EC is a FPM, and our previous research revealed that EC showed strongest cytotoxicity in three cancer models than other compounds isolated from the leaves of E. robusta. This study investigated its anti-tumor effects on human hepatocellular carcinoma (HCC) and its underlying mechanisms.

METHODS: Cell viability was measured by MTT assay. Cell cycle, apoptosis and mitochondrial transmembrane potential were determined by flow cytometry. Immunofluorescence was determined by a laser scanning confocal microscope. Protein levels were analyzed by Western blotting.

RESULTS: Our results showed that EC exerted strong anti-proliferative activity against HCC cells in a concentration- and time-dependent manner. EC markedly induced apoptosis through the caspase-dependent mitochondrial pathway, and the cell cycle was arrested at S phase. SB203580, a p38 MAPK inhibitor, effectively decreased cell death caused by EC. Moreover, the ROS scavenger N-acetyl cysteine (NAC) significantly attenuated apoptosis induced by EC and reversed EC-induced p38 MAPK activation.

CONCLUSION: Our findings indicate that EC induces mitochondrial-dependent apoptosis in HCC cells through ROS generation and p38 MAPK activation, making EC a promising candidate for further development as an anticancer agent for HCC cells.

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Sayer Ji
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