Cytotoxic and Antiproliferative Effects of Fusaric Acid on Human Prostate Cancer Cell Lines PC-3 and LNCaP

Objective: Fusaric acid (FA), a secondary metabolite derived from Fusarium species and structurally similar to picolinic acid, has recently attracted increasing interest due to its potential anticancer properties. This study aimed to investigate the cytotoxic, antiproliferative, apoptotic, and oxidative effects of FA on human prostate cancer cell lines PC-3 and LNCaP under in vitro conditions. Methods: PC-3 and LNCaP cells were exposed to increasing concentrations of FA and incubated for 48 hours. Cell viability was assessed using the XTT assay, and IC₅₀ values were calculated. Expression levels of apoptosis-related genes (CASP3, CASP8, CASP9, CASP10, BAX, BID, and BCL-2) were analyzed by quantitative real-time PCR (qRT-PCR). Proliferative and migratory behaviors were evaluated using colony formation and wound healing assays, respectively. Oxidative stress was assessed by measuring total oxidant status (TOS), total antioxidant status (TAS), and calculating the oxidative stress index (OSI). Results: The IC₅₀ values of FA were determined as 262.94 µM for PC-3 cells and 278.72 µM for LNCaP cells. FA treatment significantly increased the expression of pro-apoptotic genes, while reducing the expression of the anti-apoptotic gene BCL-2. Colony-forming capacity was markedly reduced following FA exposure, with no significant enhancement in wound closure. TOS levels significantly decreased in LNCaP cells, while OSI values declined in both cell lines. No statistically significant changes were observed in TAS levels. Conclusion: This study demonstrates that fusaric acid exerts pronounced antiproliferative and pro-apoptotic effects on prostate cancer cells, potentially through the modulation of oxidative stress. These findings support the potential use of FA as a therapeutic candidate in prostate cancer treatment.