Euphol from Euphorbia tirucalli selectively inhibits human gastric cancer cell growth through the induction of ERK1/2-mediated apoptosis |
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| Authors: | Ming-Wei Lin An-Shen Lin Deng-Chyang Wu Sophie SW Wang Fang-Rong Chang Yang-Chang Wu Yaw-Bin Huang |
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| Institution: | 1. Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC;2. Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, ROC;3. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, ROC;4. Graduate Institute of Nature Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC;5. Natural Medicinal Products Research Center and Center for Molecular Medicine, China Medical University Hospital, Taichung 402, Taiwan, ROC;6. Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 402, Taiwan, ROC |
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| Abstract: | Gastric cancer is one of the most common malignancies worldwide, and the main cause of cancer-related death in Asia. The present study assessed the anticancer effects of euphol, a triterpene alcohol with anti-inflammatory and antiviral activities on human gastric cancer cells. Euphol showed higher cytotoxicity activity against human gastric CS12 cancer cells than against noncancer CSN cells. In addition, it up-regulated the pro-apoptotic protein BAX and down-regulated the prosurvival protein Bcl-2, causing mitochondrial dysfunction, possibly by caspase-3 activation. The anti-proliferative effects of euphol were associated with the increased p27kip1 levels and decreased cyclin B1 levels. Inhibition of ERK1/2 activation by PD98059 reversed euphol-induced pro-apoptotic protein expression and cell death. Taken together, these findings suggest that euphol selectively induced gastric cancer cells apoptosis by modulation of ERK signaling, and could thus be of value for cancer therapy. |
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| Keywords: | BAX Bcl-2-associated X protein Bcl-2 B-cell lymphoma 2 ERK1/2 extra-cellular signal-regulated kinase 1/2 IC50 50% inhibitory concentration FITC fluorescein isothiocyanate MAPK mitogen-activated protein kinase PBS phosphate buffered saline p-ERK1/2 phosphorylated extra-cellular signal-regulated kinase 1/2 |
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