title: Rh2E2, a novel metabolic suppressor, specifically inhibits energy-based metabolism of tumor cells.
abstract: 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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Vincent Kam Wai
authors.initials: VK
authors.lastname: Wong
authors.affiliation: Shum 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.
authors.forename: Hang
authors.initials: H
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, New Jersey, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, New Jersey, USA.
authors.forename: Ah Ng Tony
authors.initials: AN
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Richard Kin Ting
authors.initials: RK
authors.lastname: Kam
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Betty Yuen Kwan
authors.initials: BY
authors.lastname: Law
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.|Shum 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.
authors.forename: Wendy Wen Luen
authors.initials: WW
authors.lastname: Hsiao
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Ka Man
authors.initials: KM
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Jingrong
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Rick Wai Kit
authors.initials: RW
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Jianru
authors.initials: J
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Feng Gen
authors.initials: FG
authors.lastname: Yen
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Elaine Lai Han
authors.initials: EL
authors.lastname: Leung
authors.affiliation: Shum 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.
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D016264:Dextran Sulfate; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D040901:Proteomics / Q000379:methods; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D024101:Mitochondrial Proteins; C000613467:ginsenoside Rh2 20,24-epoxide; C055305:ginsenoside Rh2; D016264:Dextran Sulfate; D001397:Azoxymethane
keywords: Rh2E2; alpha-enolase; anti-tumor; energy metabolism; metabolic suppressor