Investigation of the role of Dichloroacetate (glycolysis inhibitor) on breast cancer cell proliferation

Breast cancer is the most common cancer among women. In recent years, due to the targeting of tumor cell metabolism and a successful coadministration of DCA with conventional chemotherapy, radiotherapy, other drugs, or natural compounds has been tested in several cancer models. DCA could significantly affect cancer stem cell fraction and contribute to cancer eradication. The DCA selectively promotes mitochondria-regulated apoptosis and inhibits tumor growth in preclinical models by shifting the glucose metabolism in cancer cells from anaerobic to aerobic glycolysis. In the current study we investigated the effects of glycolysis inhibition (using DCA) on viability of breast cancer cell line ۴T۱ in vitro. ۳۰۰۰/well cells were seeded into ۹۶-well tissue culture plates. After ۴۸ hours’ incubation, we replaced media with fresh cell culture media containing increasing doses of DCA (۰.۵, ۱, ۲, ۳, ۴, ۵, ۶,۷,۸,۹ and ۱۰ mM). After ۲۴ h of incubation, we performed MTT assay by replacing the media with ۱۰ μl of MTT solution and incubated in the dark for ۳ h. MTT solution was then removed and DMSO was added to the wells. After ۳۰ min extraction at room temperature, the absorbance of the formazan solution was read spectrophotometrically at ۵۷۰ nm. Dichloroacetate (۳ mM) in cancer cell proliferation leading to reduced growth of cell line ۴T۱. Doses ۳ mM the viability rate is less than ۷۰%. At doses of ۰.۵ and ۱۰ mM, the viability rates are ۹۱% and ۵۹%, respectively. Moreover, the high doses of DCA (۰.۵, ۳, ۱۰ mM) induce a significant morphological change during the study. We have shown the breast cancer ۴T۱ cell line were highly sensitive to DCA, and dose of ۱۰ mM causing a significant inhibition of cancer cell viability and growth.

کلیدواژه ها:

۴T۱ cell line ، DCA ، MTT assay ، viability