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

Author(s)

Tuttis, Katiuska ; Thomazela Machado, Ana Rita ; De Silva Santos, Patrick Wellington ; Greggi Antunes, Lusania Maria

• Document type: Journal article
• Source: NUTRIENTS; v. 15, n. 12, p. 18-pg., 2023-06-01.

Abstract

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. (AU)

• FAPESP's process: 17/24576-0 - Effects of nutraceuticals sulforaphane, diallyl disulfide and vitamin D in human cancer cell lines: Evaluation of cytotoxicity, genotoxicity, cell migration, epigenetics changes and gene expression
• Grantee: Lusânia Maria Greggi Antunes
• Support Opportunities: Regular Research Grants