Resveratrol Modulates Apoptosis- and Cell Cycle-Related Gene Expression in Ishikawa Endometrial Cancer Cells

Background: The present study investigated the impact of resveratrol on cellular viability, apoptotic activity, proliferative capacity, and estrogen receptor/PTEN-associated signaling pathways in the ER-positive endometrial cancer cell line Ishikawa.Methods: Ishikawa cells were treated with different concentrations of resveratrol, and cell viability was assessed at 24, 48, and 72 hours using the MTT test. Based on dose-response results, sub-cytotoxic doses (15 and 30 μM) were selected for molecular studies. mRNA expression of apoptosis-related genes (BAX, BCL-2, CASP3), the proliferation marker CCND1, estrogen receptor gene ESR1, and tumor suppressor PTEN was quantified using qRT-PCR.Results: Resveratrol treatment caused a progressive, dose- and time-dependent decrease in Ishikawa cell viability. qRT-PCR analysis demonstrated upregulation of pro-apoptotic BAX and CASP3, downregulation of anti-apoptotic BCL-2 and proliferation-associated CCND1, significant suppression of ESR1, and dose-dependent elevation of PTEN expression. An increased BAX/BCL-2 ratio indicates that cellular homeostasis has shifted towards a pro-apoptotic state.Conclusion: These results indicate that resveratrol promotes pro-apoptotic transcriptional responses and reduces cell viability, potentially associated with changes in genes related to estrogen receptor signaling and PTEN pathways. The observed effects at sub-cytotoxic concentrations suggest resveratrol as a promising candidate for experimental adjunct therapy in ER-positive endometrial cancer models.