Effect Of Glucose Metabolism On Tanshinone ?A And Curcumin Inhibit The Proliferation Of Esophageal Cancer Cell

Natural products represent an important source for novel molecules with anti-cancer properties. The emerging interplay between cancer cell metabolism and other hallmarks of cancer raises the question whether or not anti-cancer activities associated with natural compounds can be attributed to changes in cancer metabolism.The subject was to observe whether or not natural products curcumin and tanshinone? A can inhibit tumor growth through the glycolytic pathway, thereby inhibiting tumor cell proliferation.Curcumin inhibited Ec109 cell growth and induced G2/M cell cycle arrest in a dose-dependent manner. In this study, curcumin down-regulated m RNA and protein expression of key glycolytic enzymes, including GLUT4, HK2, PFKBP3, and PKM2.Curcumin caused a significant AMPK activation in Ec109 cells in a concentrationdependent manner. The AMPK activator AICAR potentiated curcumin-mediated down-regulation of glycolytic enzymes in Ec109 cells. Whereas the AMPK inhibitor compound C reversed curcumin-mediated down-regulation of glycolytic enzymes in Ec109 cells. Importantly, si RNAs targeting AMPK significantly reversed the curcumin-mediated down-regulation of glycolytic enzymes in Ec109 cells. GLUT4-,HK2-, PFKFP3-, and PKM2-knockdown Ec109 cells exhibited decreased cell proliferation, whereas AMPK-knockdown Ec109 cells exhibited increased cell proliferation. It was suggested that the AMPK-regulated glycolytic enzymes play an important role in controlling Ec109 cell growth.Tanshinone ? A treatment reduced cancer cell viability and induced cell cycle arrest in S phase. In this study, tanshinone ?A down-regulated m RNA and protein expression of key glycolytic enzymes, including GLUT4, HK2, PFKBP3, and PKM2.PKM2-knockdown by si RNA potentiated tanshinone ? A-induced a significant decrease in PKM2 m RNA and protein expression in Ec109 cells. Target Scan databases led to the identification of mi R-122 for targeting PKM2, the m RNA and the protein expression of PKM2 were significantly down-regulated in mi R-122mimics-transfected cells, as confirmed by RT-PCR and Western blot analysis,respectively. Whereas knockdown of mi R-122 by mi R-122 inhibitor increased the m RNA and the protein expression of PKM2 in Ec109 cells. Moreover, mi R-122 mimics potentiated tanshinone ? A-induced PKM2 m RNA and protein down-regulation; whereras mi R-122 knockdown prevented the tanshinone ?A-induced PKM2 m RNA and protein downregulation. These data indicated that mi R-122 inhibited PKM2 expression and was responsible for tanshinone?A-induced PKM2 down-regulation. Tanshinone ? A treatment reduced cancer cell viability through mi R122-medated PKM2 down-regulation. These findings altogetherindicated that mi R-122 functioned on growth inhibition in part through targeting PKM2 in Ec109 cells.In conclusion, targeting of metabolic alterations could promote the reversion to a normal cell metabolism should prevent cancer formation. This suggests the metabolic pathways are attractive targets for possible therapeutic interventions in cancer prevention.