COMPARATIVE EFFECTS OF RESVERATROL AND CAFFEIC ACID ON CELL VIABILITY, APOPTOSIS, AND PTEN/AKT1 SIGNALING IN MCF-7 BREAST CANCER CELLS

Abstract

Objective: This study evaluates the effects of resveratrol and caffeic acid on viability, proliferation, and apoptosis in ER⁺ MCF-7 breast cancer cells, with additional analysis of PTEN/AKT1-related transcriptional changes. Methods: MCF-7 cells were exposed to resveratrol at concentrations ranging from 5 to 50 µM and to caffeic acid at concentrations of 10 to 50 µM for incubation periods of 24, 48, and 72 h. Cell viability was assessed using the MTT assay. The expression levels of apoptosis-related genes (BAX, BCL-2, and CASP3), the proliferation marker CCND1, the estrogen receptor gene ESR1, and signaling pathway-related genes (PTEN and AKT1) were analyzed by quantitative real-time PCR. The BAX/BCL-2 ratio was calculated as an indicator of mitochondrial apoptotic balance. Results: Resveratrol treatment resulted in a significant, dose- and time-dependent reduction in MCF-7 cell viability compared with the control group (p0.05). At higher concentrations, resveratrol significantly upregulated the pro-apoptotic genes BAX and CASP3, while concurrently reducing BCL-2 expression, resulting in a marked increase in the BAX/BCL-2 ratio. In contrast, caffeic acid induced similar but less pronounced changes. Resveratrol significantly downregulated CCND1 and ESR1 expression at early time points and increased PTEN expression while reducing AKT1 expression after 48 hours, suggesting transcriptional regulation of the PTEN/AKT1 signaling pathway. Conclusion: These findings demonstrate that resveratrol exerts stronger anti-proliferative and pro-apoptotic effects than caffeic acid in ER⁺ MCF-7 breast cancer cells. The biological effects of resveratrol appear to be associated with the regulation of mitochondrial apoptosis and the PTEN/AKT1 signaling axis, supporting its potential role as a complementary therapeutic candidate in ER-positive breast cancer.