Potentiation of paclitaxel antitumor activity by galloflavin or oxamate as lactate dehydrogenase inhibitors

Document Type : Original Article

Authors

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.

Abstract

Increased aerobic glycolysis in cancer, a phenomenon known as the Warburg effect, has been observed in various tumor cells and represents a major biochemical alteration associated with malignant transformation. Several human cancers display elevated expression of Lactate dehydrogenase-A (LDH-A) which is involved in tumor initiation, maintenance, and progression. Significantly, the inhibition of LDH-A has been reported to have an antiproliferative effect on breast tumor and inhibit tumor progression. Accordingly, several LDH-A inhibitors are being tested for their anticancer activity such as oxamate and galloflavin. Both oxamate and galloflavin anti-tumor activity was tested in vitro using MCF7 and OVCAR-3 human carcinoma cell lines. Furthermore, both drugs were examined in combination with paclitaxel (Taxol) chemotherapy in vitro. Additionally, the potential anti-tumor effect of oxamate in Solid Ehrlich Carcinoma (SEC) mouse model was examined alone and in combination with paclitaxel chemotherapy. Oxamate and galloflavin caused a significant reduction in the cell survival of MCF7 and OVCAR3 cell lines. They also caused significant reduction in LDH enzyme level and ATP cellular content in addition to significant increase in MDA content. Both oxamate and galloflavin potentiated the anti-cancer effect of paclitaxel both in vivo and in vitro. Moreover, potentiation of apoptosis and anti-angiogenic effect of paclitaxel by oxamate was found in vivo.
In conclusion, LDH inhibitor may represent a promising agent that enhances the antitumor activity of paclitaxel chemotherapy.

Keywords

Main Subjects

Journal of Advanced Medical and Pharmaceutical Research
Volume 2, Issue 2
September 2021
Pages 64-76

Files

Share

How to cite

Statistics