| Cancer stem cells obtain energy demand through the activation of glycolysis and lipolysis. It seems that the use of
approached targeting glycolysis and lipolysis could be an efective strategy for the inhibition of cancer stem cells.
In the current experiment, we studied the potential efect of glycolysis and lipolysis inhibition on cancer stem cells
diferentiation and mesenchymal–epithelial-transition capacity. Cancer stem cells were enriched from human ovarian
cells namely SKOV3 by using MACS technique. Cells were exposed to Lonidamine, an inhibitor of glycolysis, and TOFA,
a potent inhibitor of lipolysis for 7 days in endothelial diferentiation medium; EGM-2 and cell viability was studied by
MTT assay. At the respective time point, the transcription level of genes participating in EMT such as Zeb-1, -2, Vimentin, Snail-1, -2 and VE-cadherin were measured by real-time PCR analysis. Our data noted that the inhibition of lipolysis
and glycolysis could decrease cell viability compared to the control of cancer stem cells. The inhibition of glycolysis
prohibited the expression of Zeb-1, Snails, and Vimentin while increased endothelial diferentiation rate indicated by
the expression of VE-cadherin. In contrast, the inhibition of lipolysis increased EMT associated genes and reduced
endothelial diferentiation rate by suppressing the transcription of VE-cadherin. Notably, the simultaneous inhibition of
glycolysis and lipolysis had moderate efects on the transcription of EMT genes. We concluded that the modulation of
the metabolic pathway of glycolysis in ovarian CSCs is more efective than the inhibition of lipolysis in the control of
angiogenesis potential and stemness feature. |