Abstract

EFFECTS OF ANTIMETABOLITES ON (MDA AND MCF 7) BREAST CANCER CELLS

Srishti Kala*, Stacey Sammons, Pratima Pandey and Omar Bagasra

ABSTRACT

It is known that cancer cells consume 200 times more glucose than normal cells and prefer aerobic glycolysis to a more efficient oxidative phosphorylation, acquiring 95% of their energy from glycolysis and a mere 5% from anaerobic tricarboxylic acid cycle. Since cancer cells display a greater sensitivity to glucose deprivation-indeed cytotoxicity than normal cells, inhibitors that interrupt glycolytic pathways, glucose cellular uptake and oxidative metabolism are logical targets in cancer treatment. Thus, we propose partial uncoupling of the mitochondrial aerobic pathways and various enzymes linked to the glycolytic pathway using two antimetabolites; amygdalin and dichloroacetate (DCA), with the immune system still intact to carry out its normal immune functions including anti-cancer and immune surveillance of neoplastic cells. We propose to develop novel drug that preferentially target cancer cells which can quell the Warburg effect without harming normal cells. The antimetabolites have known toxicity against cancer which when combined can create a synergistic effect in the treatment of cancer. Here we show that both amygdalin and DCA significantly alter the metabolic pathways of two breast cancer cell lines, when used alone and most importantly when combined at the same time. In the presence of these anti metabolite cells use alternate carbon sources like L-Arabinose, L-Fucose etc. to survive. Combining both antimetabolites, can be an effective alternative to chemotherapy and radiation therapy which lead to increased chances of secondary resistant cancers.

Keywords: Amygdalin, antimetabolite, beta-glucosidase, cancer, cyanide, dichloroacetate, glycolysis, oxidative phosphorylation, breast, rhodanese, Warburg effect.