2-Methoxyestradiol Reverses the Pro-Carcinogenic Effect of L-Lactate in Osteosarcoma 143B Cells

Abstract

Background/aim: According to the reverse Warburg effect, tumor cells may metabolize lactate as an energy source and shuttle L-lactate to neighboring cancer cells, adjacent stroma, and vascular endothelial cells, thus inducing metabolic reprogramming. An increased tumor L-lactate level strictly correlates with increased metastasis, tumor recurrence and a poor outcome. A potent anticancer agent that may act on L-lactate activated cells is 2-metoxyestradiol. Thus, the aim of the study was to evaluate whether a potent anticancer agent, 2-methoxyestradiol, is able to reverse L-lactate-induced metabolic reprogramming in osteosarcoma 143B cells.

Materials and methods: We used flow cytometry in order to determine cell death, autophagy, expression of KI-67, mitochondrial membrane depolarization. We performed cell proliferation assay in order to determine cell viability and cell migration assay to determine invasive potential of osteosarcoma cells. While, CalcuSyn software was used in order to evaluate the interaction between 2-methoxyestradiol and L-lactate.

Results: We demonstrated that 2-methoxyestradiol abolished L-lactate-induced migration and proliferation of osteosarcoma cells. Moreover, we observed that this effect was associated with regulation of Ki-67 and induction of autophagy.

Conclusion: 2-Methoxyestradiol is a potent anticancer agent also under metabolic reprogramming conditions.

Keywords: 2-Methoxyestradiol; L-lactate; osteosarcoma; tumor microenvironment.