GALLIC ACID IN COMBINATION WITH CISPLATIN TRIGGERED APOPTOSIS IN MCF-7 BREAST CANCER CELLS

Abstract

Breast cancer emerges as the most prevalent malignancy among women worldwide. While single-agent chemotherapy is commonly used in cancer treatment, combination therapy is generally considered more effective. Cisplatin is effective against a broad spectrum of cancers, though several drawbacks limit its clinical use. Combination treatment has proven to overcome these limitations, which involves pairing conventional drugs with natural compounds. Gallic acid exhibits potent antioxidant and anticancer activities, making it a potential candidate for such combinations. Therefore, this study aims to determine the effect of gallic acid combined with cisplatin on the proliferation of breast cancer cells (MCF-7) through apoptosis induction, characterised by the apoptotic morphology of the treated cells. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to determine the minimal inhibitory concentration at 50% of cell populations (IC₅₀). The IC₅₀ value of gallic acid was combined with cisplatin and applied to the cells to obtain the combination index (CI) value using CompuSyn software. Apoptotic morphology was investigated using AO/PI staining and visualised under a fluorescence microscope. Gallic acid and cisplatin showed potent IC₅₀ (< 20 µg/mL) which were 9.765 µg/mL and 0.7869 µg/mL, respectively. A fixed concentration of gallic acid (9.765 µg/mL) combined with cisplatin at concentrations of 0.09836 µg/mL and 0.04918 µg/mL yielded CI values of 0.97423 and 0.65164 indicating a synergistic effect. Apoptotic features were observed morphologically in both single and combined treatments, with a higher number of apoptotic cells noted in the combined treatment, as indicated by bright green and orange fluorescence. This proves the potency of gallic acid in enhancing the antiproliferative effect of cisplatin against MCF-7 cells. In conclusion, a combination of gallic and cisplatin suppressed the MCF-7 cell proliferation through the induction of apoptosis.