Rh2E2, a novel metabolic suppressor, specifically inhibits energy-based metabolism of tumor cells
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Vincent Kam Wai Wong1,*, Hang Dong2,*, Xu Liang1,*, Li-Ping Bai1, Zhi-Hong Jiang1, Yue Guo3, Ah-Ng Tony Kong3, Rui Wang1, Richard Kin Ting Kam1, Betty Yuen Kwan Law1, Wendy Wen Luen Hsiao1,2, Ka Man Chan1, Jingrong Wang1, Rick Wai Kit Chan1, Jianru Guo1, Wei Zhang1, Feng Gen Yen1, Hua Zhou1, Elaine Lai Han Leung1, Zhiling Yu2, Liang Liu1
1State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China
2Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
3Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, New Jersey, USA
*These authors have contributed equally to this work
Liang Liu, e-mail: [email protected]
Keywords: Rh2E2, metabolic suppressor, alpha-enolase, energy metabolism, anti-tumor
Received: September 02, 2015 Accepted: December 26, 2015 Published: January 18, 2016
Energy metabolism in cancer cells is often increased to meet their higher proliferative rate and biosynthesis demands. Suppressing cancer cell metabolism using agents like metformin has become an attractive strategy for treating cancer patients. We showed that a novel ginsenoside derivative, Rh2E2, is as effective as aspirin in preventing the development of AOM/DSS-induced colorectal cancer and suppresses tumor growth and metastasis in a LLC-1 xenograft. A sub-chronic and acute toxicity LD50 test of Rh2E2 showed no harmful reactions at the maximum oral dosage of 5000 mg/kg body weight in mice. Proteomic profiling revealed that Rh2E2 specifically inhibited ATP production in cancer cells via down-regulation of metabolic enzymes involving glycolysis, fatty acid β-oxidation and the tricarboxylic acid cycle, leading to specific cytotoxicity and S-phase cell cycle arrest in cancer cells. Those findings suggest that Rh2E2 possesses a novel and safe anti-metabolic agent for cancer patients by specific reduction of energy-based metabolism in cancer cells.
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