Prenylated Stilbenoids as Potential Adjuvants for Paclitaxel in the Treatment of Triple‐Negative Breast Cancer

Abstract

Breast cancer is the most prevalent type of cancer among women worldwide. Triple‐negative breast cancer (TNBC) is unresponsive to typical hormonal treatments causing it to be one of the deadliest forms of breast cancer. Investigating alternative therapies to increase survival rates for this disease is essential. This study aims to examine the role of prenylated stilbenoids as an adjuvant for paclitaxel, a chemotherapeutic drug with severe side effects. To produce prenylated stilbenoids, hairy root cultures of peanut were co‐treated with elicitors and further purified via semi‐preparative high performance liquid chromatography. The cytotoxicity of prenylated stilbenoids was studied in TNBC cell lines MDA‐MB‐231 and MDA‐MB‐436 and the non‐cancerous cell line MCF‐10A. At low micromolar concentrations, the prenylated stilbenoid arachidin‐1 showed no significant cytotoxicity in the non‐cancerous cell line, whereas it was cytotoxic in the TNC cell lines. High cytotoxicity levels correlated with increased levels of the apoptosis markers caspase‐3 and caspase‐7. Arachidin‐1 also decreased the IC50 of paclitaxel by approximately 4‐fold and blocked cell division in S and G2‐M phases in the TNBC cells. Furthermore, paclitaxel combined with arachidin‐1 induced apoptosis through the intrinsic pathway by activation of caspase‐9. This highlights the significance of continuing research with prenylated stilbenoids in TNBC. Current studies focus on elucidating the signaling pathways affected by these compounds in TNBC cells to advance our understanding of the anticancer mechanisms of these natural products.