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Oncotarget ; 7(9): 9907-24, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26799418

RESUMO

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 ß-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.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Metabolismo Energético/efeitos dos fármacos , Ginsenosídeos/farmacologia , Neoplasias/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Azoximetano , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Sulfato de Dextrana , Medicamentos de Ervas Chinesas/química , Ginsenosídeos/química , Humanos , Immunoblotting , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Estrutura Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Proteômica/métodos , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos
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