Replacement of hydrochloride in metformin hydrochloride with caprylic acid to investigate its effects on MCF-7 and MDA-MB-231 breast cancer cell lines.

AIMS: Metformin hydrochloride is a highly hydrophilic molecule with low permeability. In the present study, to develop an effective drug to treat the metastatic breast cancer, metformin caprylic acid was synthesized using metformin hydrochloride as a permeable agent. MAIN METHODS: The cytotoxic effects of various concentrations of metformin caprylic acid and metformin hydrochloride (0 to 20 mM) on MCF-7 and MDA-MB-231 breast cancer cells and MCF-10A human mammary epithelial cell line were assessed by the MTT assay. Furthermore, Annexin V, PI staining, and cell flow cytometry assays were performed to evaluate the apoptotic effects. The invasion and migration ability of these cells were evaluated following treatment with equal concentration (3 mM) of the two compounds. KEY FINDINGS: The treatment of tested cell lines with an equal concentration of two chemicals decreased cell viability in a time and dose-dependent manner, where in all cases, metformin caprylic acid caused significantly more apoptosis and invasion inhibition than that of metformin hydrochloride (*p < 0.05). Chemical structures of both compounds were confirmed by FTIR and 1H NMR, 13C NMR. Both chemicals inhibited the migration of MCF-7 and MCF-10A cells, but had no effect on MDA-MB-231 migration. All data are expressed as mean ± SD (n = 3). SIGNIFICANCE: It seems that in an equal concentration, the similarity of the hydrophobic tail of caprylic acid to the cell membrane improves its entrance, while decreasing the drug excretion.