Sulforaphane Combined with Vitamin D Induces Cytotoxicity Mediated by Oxidative Stress, DNA Damage, Autophagy, and JNK/MAPK Pathway Modulation in Human Prostate Tumor Cells.

Autor: Tuttis K; Department of Genetics, Ribeirão Preto School of Medicine, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil., Machado ART; Department of Clinical Analysis, Toxicology, and Food Sciences, Ribeirão Preto School of Pharmaceutical Sciences, University of São Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil., Santos PWDS; Department of Clinical Analysis, Toxicology, and Food Sciences, Ribeirão Preto School of Pharmaceutical Sciences, University of São Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil., Antunes LMG; Department of Clinical Analysis, Toxicology, and Food Sciences, Ribeirão Preto School of Pharmaceutical Sciences, University of São Paulo-USP, Ribeirão Preto 14040-903, SP, Brazil.
Jazyk: angličtina
Zdroj: Nutrients [Nutrients] 2023 Jun 14; Vol. 15 (12). Date of Electronic Publication: 2023 Jun 14.
DOI: 10.3390/nu15122742
Abstrakt: Prostate cancer ranks second in incidence worldwide. To date, there are no available therapies to effectively treat advanced and metastatic prostate cancer. Sulforaphane and vitamin D alone are promising anticancer agents in vitro and in vivo, but their low bioavailability has limited their effects in clinical trials. The present study examined whether sulforaphane combined with vitamin D at clinically relevant concentrations improved the cytotoxicity of the compounds alone towards DU145 and PC-3 human prostate tumor cells. To assess the anticancer activity of this combination, we analyzed cell viability (MTT assay), oxidative stress (CM-H 2 DCFDA), autophagy (fluorescence), DNA damage (comet assay), and protein expression (Western blot). The sulforaphane-vitamin D combination (i) decreased cell viability, induced oxidative stress, DNA damage, and autophagy, upregulated BAX, CASP8, CASP3, JNK, and NRF2 expression, and downregulated BCL2 expression in DU145 cells; and (ii) decreased cell viability, increased autophagy and oxidative stress, upregulated BAX and NRF2 expression, and downregulated JNK, CASP8, and BCL2 expression in PC-3 cells. Therefore, sulforaphane and vitamin D in combination have a potential application in prostate cancer therapy, and act to modulate the JNK/MAPK signaling pathway.
Databáze: MEDLINE