Effect of ganoderic acid D on colon cancer Warburg effect: Role of SIRT3/cyclophilin D

Ganoderic acid D (GAD) is a highly oxygenated tetracyclic triterpenoid. This study aims to assess the effects of GAD on the energy metabolism of colon cancer through the regulation of SIRT3 expression and whether this effect is related to acetylated cyclophilin D. The results demonstrated that GAD inhibits the energy reprogramming of colon cancer cells including glucose uptake, lactate production, pyruvate and acetyl-coenzyme production in colon cancer cells. Meanwhile, GAD upregulated the protein expression of SIRT3. Furthermore, the interruption of SIRT3 expression significantly reversed all the effects of SIRT3 on the energy reprogramming of colon cancer. In addition, GAD induced the deacetylated cyclophilin D (CypD) by SIRT3, whereas SIRT3-shRNA inhibited its combining effect on CypD. The energy reprogramming effects of GAD on colon cancer seem to be mediated by SIRT3 upregulation via acetylated CypD inhibition.