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Does docosahexaenoic acid interfere with the response of prostate tumor cells to enzalutamide?

Grant number: 22/07684-1
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2022
Effective date (End): August 31, 2024
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Rejane Maira Góes
Grantee:Laurielle do Prado Ferreira
Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Prostate Cancer (PCa) is a major public health problem, especially castration-resistant cancer (CRPC), whose treatment is still challenging. Experimental evidence indicates that consumption of the omega-3 (É-3) polyunsaturated fatty acid - docosahexaenoic acid (DHA) - reduces the risk of PCa, but this issue is still controversial in epidemiological studies. We have found that DHA delays tumor progression in transgenic mice for prostate cancer in its early stages. We also found that this É-3 reduces the survival of human prostate cells by differential mechanisms in pre-malignant and tumor cells. Although the antitumor action of DHA is complex and involves multiple mechanisms, both in vivo and in vitro studies demonstrate that this É-3 interferes with androgen receptor (AR) signaling and other signaling pathways that are dysregulated in the CRPC. Many of these pathways are also regulated by Enzalutamide, a second-generation, non-steroidal AR inhibitor used in the treatment of CRPC. In the present study, we will examine whether DHA interferes with the response of castration-resistant prostate tumor cells (22Rv1) to the anticancer drug Enzalutamide. The following will be evaluated: (1) cell proliferation/survival rates (MTS assays and Trypan blue exclusion method); (2) the rate of apoptosis (a colorimetric assay for proteolytic activity of activated caspase-3) and (3) protein expression of AR-FL, AR-V7 variant and GR (Western blotting). This project will clarify whether DHA acts synergistically with this drug in this cell tumor lineage and provide experimental indications for its use as an adjuvant in the treatment of CRPC.(AU)

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