Stilbene-rich extract increases the cytotoxic effects of paclitaxel in hormone receptor-positive and triple-negative breast cancer spheroids

Abstract

BackgroundTriple-negative breast cancer (TNBC) is an aggressive form of breast cancer that lacks three receptors commonly found in breast cancer cells. It is associated with high mortality rates, and therefore, investigating therapies to increase survival rates is crucial. Plant-derived compounds are being explored as potential adjuvants for common chemotherapy drugs, such as paclitaxel (Pac). PurposeThe study aimed to evaluate the cytotoxic effect of a prenylated stilbene-rich extract (SRE) produced via a sustainable peanut hairy root culture system and observe its potential as an adjuvant for Pac in human triple-negative and hormone receptor-positive (HR+) breast cancer spheroids. The effects were compared to arachidin-1 (A-1), a cytotoxic prenylated stilbene present in the extract. MethodsSRE was produced from elicited peanut hairy root cultures. The extract was purified using chromatography techniques to obtain the prenylated stilbene arachidin-1 (A-1) with a purity of over 95%. TNBC cell lines MDA-MB-231, MDA-MB-436, and HR+ breast cancer cell line MCF-7 were used to evaluate the cytotoxicity and apoptotic activity of SRE in comparison with A-1. Two-dimensional (2D) experiments were performed using cell viability assays and imaging microscopy. Three-dimensional (3D) spheroids cultures were established, and the impact of SRE alone and in combination with Pac on cell viability and caspase 3/7 activity was evaluated. ResultsSRE (10 μg/mL) inhibited cell proliferation by approximately 50% in TNBC and MCF-7 cells in a time-dependent manner. Additionally, Annexin V FITC/PI staining revealed that SRE (10 μg/mL) induced more apoptosis than A-1 at the equimolar concentration (5 μM) in MDA-MB-231 cells. Combining SRE with Pac decreased spheroid cell viability and induced apoptosis by activating caspases 3 and 7 in TNBC and HR+ breast cancer spheroids. ConclusionsThese findings highlight the potential of SRE as a novel adjuvant for Pac chemotherapy in TNBC and HR+ breast cancer treatment.