In Vitro Evaluation of the Combined Effects of Rosmarinic Acid and 5-Fluorouracil in Prostate Cancer Cells

INTRODUCTION: Prostate cancer is the most common malignancy in men. Despite therapeutic advances, drug resistance remains a major challenge, and many patients progress to castration-resistant prostate cancer (CRPC). This study aims to investigate the combined effects of rosmarinic acid (RA), a polyphenolic compound, and 5-FU, a conventional chemotherapeutic agent, on DU145 prostate cancer cells.
METHODS: Cell viability was assessed at various doses for RA and 5-FU to determine the IC50, IC30, and IC10 values. For combination studies, IC30 dose was selected, and the effects of the treatments were evaluated using MTT assays, colony formation assays, scratch healing assays and acridine orange/ethidium bromide staining assays.
RESULTS: Monotherapy with RA and 5-FU demonstrated a dose-dependent inhibitory effect on cell viability. The combination of both agents at their IC30 concentrations produced a statistically significant and combined inhibition of colony formation and cell motility compared to the single-agent and control groups. Furthermore, combined treatment induced more pronounced changes in characteristic cell morphology associated with apoptosis and necrosis than monotherapy groups.
DISCUSSION AND CONCLUSION: This study presents preliminary findings on the combined effects of rosmarinic acid with 5-fluorouracil. The combination significantly suppressed cell viability, colony formation capacity, and motility in CRPC cells in vitro and increased apoptosis- and necrosis- associated cell death compared to single treatments. In conclusion, these in vitro results suggest that combining the chemotherapeutic agent 5-FU with the natural compound RA may enhance treatment efficacy and represent a promising strategy for managing castration-resistant prostate cancer.

Keywords: 5-Fluorouracil, Drug Combinations, Prostate Cancer, Rosmarinic Acid