Co-drug development of gallic acid and metformin targeting the pro-inflammatory cytokines for the treatment of breast cancer.

It is well-documented that pro-inflammatory cytokines and inflammation play a significant role in the expansion of cancer disease. Gallic acid (GA), a natural compound, and metformin (Met), a synthetic drug exhibit potent anticancer potential via the distinct molecular mechanism. However, whether both these compounds can act synergistically to preclude and treat cancer is still unknown. This prompted us to scrutinize, the synergism between GA and Met, and that of a new co-drug synthesizing of GA and Met (GA-Met) and investigated the chemo-protective effect against breast cancer with possible intervention of cytokines. In vivo studies were based on chemical carcinogenesis, challenging breast tissue by dimethylbenz[α]anthracene (DMBA). Tumour incidence, tumour burden, pro-inflammatory cytokines in serum, breast, hepatic tissue, macroscopically and histological analysis of mammary tumours were carried out and estimated. GA, Met and GA-Met co-drug exhibited the inhibition of cell proliferation; higher reduction of cell proliferation was observed by GA-Met. The inhibitory effect of GA-Met was linked to cell cycle arrest at G0/G1 phase, along with induction of apoptosis and accumulation in the sub-G1 phase. GA-Met significantly inhibited the cytokines production along with protection against DMBA-induced hyperplasia. Taken altogether, the current result suggests that GA-Met co-drug endows a safe and protective effect against cancer metastasis and can possibly use for the treatment of human breast cancer.