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Enhancing Prostate Cancer Cells’ Sensitivity to Flutamide by Resveratrol: An In-Vitro Study Publisher Pubmed



Hosseini SF1 ; Yahyazadeh SR2 ; Mirzaei A1 ; Mashhadi R1 ; Ghajar HA1 ; Taheri D1, 3 ; Aghamir SMK1
Authors
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Authors Affiliations
  1. 1. Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Urology, Shariati Hospital, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pathology, Isfahan Kidney Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Tissue and Cell Published:2025


Abstract

Background: As the most common cancer in men, and its progression poses a significant challenge. New and effective treatment strategies are needed to improve outcomes for patients with prostate cancer. This study examined if resveratrol, a natural substance, could improve prostate cancer cell lines' response to flutamide, a standard antiandrogenic treatment for untreated prostate cancer, while minimizing adverse effects. Method: MTT assay was used to quantify resveratrol and flutamide IC50 values, Annexin-V/PI staining for apoptosis, PI staining for DNA cell cycle, and real-time PCR for BAX, BCL-2, VEGFC, HIF-1α, Snail1, E-Cadherin, and KLK3 mRNA levels Scratch-wound, colony-forming, and Hoechst staining analyzed cell migration, proliferation, and nucleus morphology. Spheroid creation in 3D was also considered. All tests used LNCaP, DU145, and PC3 prostate cancer cell lines at various stages. Results: Resveratrol, when combined with flutamide, can reduce malignant cell migration, colony formation, and proliferation and promote apoptosis in prostate cancer cell lines. Even in androgen-unresponsive cell lines (DU145 and PC3), it may benefit flutamide prostate cancer treatment. Apoptosis genes (BAX) were upregulated in LNCaP, DU145, and PC3 cancer cell lines when administered alone or with flutamide. Additionally, flutamide might significantly lower BCL-2 levels in PC3 cells. When combined with flutamide, resveratrol increased apoptosis and altered the expression of genes involved in angiogenesis (VEGFC), epithelial-mesenchymal transition (EMT, Snail1 and E-Cadherin), and prostate cancer biomarker (KLK3) in prostate cancer cell lines. Conclusion: Resveratrol reduced the dose of flutamide in the treatment of prostate cancer cell lines (LNCaP, DU145, and PC3) and improved its side effects, as well as increasing the sensitivity of cells to flutamide treatment. © 2025 Elsevier Ltd
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