Antiproliferative Effects of Reynoutrin via Modulation of Oxidative Stress, Inflammation, and Apoptosis in Breast...

Reynoutrin, a bioactive flavonoid, exhibits various biological effects. Despite its toxic side effects, cisplatin is widely used to treat malignancies. This study aimed to assess the in vitro antiproliferative activity of reynoutrin in MCF-7 and PC-3 cell lines by evaluating its effects on inflammation, oxidative stress, and apoptosis-related pathways. The cytotoxic effects of reynoutrin on MCF-7 and PC-3 cells were evaluated using an MTT assay after 24 h. Total antioxidant status (TAS) and total oxidant status (TOS) were measured using ELISA kits. The mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, caspase-3, caspase-9, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were analyzed by RT-qPCR. Apoptotic morphological changes were assessed by Hoechst staining. Reynoutrin inhibited MCF-7 and PC-3 cell viability in a dose-dependent manner, with IC₅₀ values of 220 and 412 µg/mL, respectively. Reynoutrin increased TOS and decreased TAS (p < 0.05), indicating an increase in oxidative stress. RT-qPCR showed that TNF-α, IL-1β, and IL-6 mRNA expression levels decreased in a dose-dependent manner following reynoutrin treatment in MCF-7 and PC-3 cells (p < 0.05), suggesting anti-inflammatory effects. In both cancer cell lines, reynoutrin increased caspase-3 and caspase-9 mRNA expression levels and decreased the Bcl-2/Bax expression ratio in a dose-dependent manner (p < 0.05). These findings suggest that reynoutrin exerts antiproliferative effects that are associated with modulation of inflammatory, oxidative stress, and apoptosis-related pathways in cancer cells, highlighting its potential as a natural candidate for further investigation as an anticancer agent.