Enhancing prostate cancer cells’ sensitivity to flutamide by resveratrol: An in-vitro study

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-02-21 DOI:10.1016/j.tice.2025.102807

Seyedeh Fatemeh Hosseini , Seyed Reza Yahyazadeh , Akram Mirzaei , Rahil Mashhadi , Helia Azodian Ghajar , Diana Taheri , Seyed Mohammad Kazem Aghamir

{"title":"Enhancing prostate cancer cells’ sensitivity to flutamide by resveratrol: An in-vitro study","authors":"Seyedeh Fatemeh Hosseini , Seyed Reza Yahyazadeh , Akram Mirzaei , Rahil Mashhadi , Helia Azodian Ghajar , Diana Taheri , Seyed Mohammad Kazem Aghamir","doi":"10.1016/j.tice.2025.102807","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Method</h3><div>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 <em>BAX, BCL-2,</em> VEGFC, <em>HIF-1α</em>, <em>Snail1</em>, <em>E-Cadherin</em>, and <em>KLK3</em> 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.</div></div><div><h3>Results</h3><div>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 (<em>BAX</em>) were upregulated in LNCaP, DU145, and PC3 cancer cell lines when administered alone or with flutamide. Additionally, flutamide might significantly lower <em>BCL-2</em> levels in PC3 cells. When combined with flutamide, resveratrol increased apoptosis and altered the expression of genes involved in angiogenesis (VEGFC), epithelial-mesenchymal transition (<em>EMT, Snail1</em> and <em>E-Cadherin</em>), and prostate cancer biomarker (<em>KLK3</em>) in prostate cancer cell lines.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102807"},"PeriodicalIF":2.7000,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040816625000874","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.