Effects of energy regulation on cell survival in breast cancer cells

Aim: The cancer increases the oxidized NAD phosphate (NADP+) pool by continuously synthesizing nicotinamide adenine dinucleotide (NAD) due to the growth of nicotinamide phosphoribosyltransferase (NAMPT). Reductive NADP (NADPH) is produced via the pentose phosphate pathway (PFY), which is induced in breast cancer. Targeting NAD metabolism may help manage energy regulation for survival. Material and Method: MCF7 and MDAMB231 cells were split into four groups after growth. MCF7-CG and MDAMB231-CG received no treatment. MCF7-FG and MDAMB231-FG were treated with 10 mM FK866, MCF7-QG, and MDAMB231-QG with 40 mM quercetin, and MCF7-AG and MDAMB231-AG with 10 mM apigenin. The following day, cells were separated from their growth medium. Measurements were taken for NAD/NADH ratio, reactive oxygen species (ROS), glutathione-s-transferase (GST) activities, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, TRPC 1 and TRPC 4 protein levels, and ER stress markers. The findings were analyzed using appropriate statistical methods. Results: Apigenin and quercetin increased NAD levels in both cell lines, but a decrease was noted in cells given FK866. Apigenin was more effective in protecting NAD, while quercetin enhanced antioxidant defense. Significant differences in IL-1β, TNF α, TRPC 1, TRPC4, GRP78, ATF4, CHOP, and caspase three levels were found between groups in both MCF7 and MDAMB231 cells (p<0.05). Conclusion: Targeting the NAD molecule, crucial for cellular energy metabolism, can deplete calcium stores in breast cancer, leading to oxidative damage and ER stress and potentially preventing malignancy. According to our findings, tumoral activity can be managed with drugs that can be developed directly targeting the calcium channels of tumor cells.