MOLECULAR MECHANISIMS UNDERLYING THE ANTI-CANCER ACTIVITY OF GUM ARABIC FROM ACACIA SP. IN TRIPLE-NEGATIVE BREAST CANCER CELLS

Metastatic breast cancer is the leading cause of cancer-related deaths among women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive, accounting for 15-20% of all breast cancer cases. As TNBC cells lack the expression of hormone receptors estrogen receptors (ER) and progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2), TNBCs are unresponsive to hormonal therapy and often become highly resistant when exposed to standard chemotherapy, which has been identified as a major obstacle in TNBC treatment. Gum Arabic, a natural exudate produced from plants, is widely used traditionally for religious, cosmetics as well as medicinal purposes for ages. Although it is well reported for its biological activities and medical value, no studies have been carried out to assess its anticancer potential. In search of new and novel compounds to target TNBCs effectively and with less toxicity, this study aims to evaluate the anticancer activity of Gum Arabic extract (GAE) against breast cancer MDA-MB-231 cell line, a triple-negative human breast cancer cell line, and to elucidate the molecular targets underlying its mechanism of action. The results revealed that GAE inhibits cell proliferation in a concentration- and time-dependent manner. The antiproliferative effect of GAE was found to be linked to cell cycle arrest at the G1/S phase along with induction of apoptosis confirmed in the cells as suggested by caspase 3/7 activation and cleaved caspase 3 and cleaved PARP detection. Cell cycle inhibitory protein p21WAF1 was increased in GAE-treated cells compared to untreated cells while cyclin D1 and c-myc were downregulated. Furthermore, the study found that Wnt/β-catenin signalling was markedly inhibited and could induce loss of expression of the canonical Wnt-directed targets genes cyclin D1, c-myc, and survivin in MDA-MB-231 cells treated with GAE. In conclusion, GAE inhibits the proliferation of MDA-MD-231 breast cancer cells that is associated with the suppression of Wnt/β-catenin signalling suggesting that Gum Arabic could be a potential new chemotherapeutic agent against highly chemo resistant triple negative breast