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

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...

Full description

Saved in:
Bibliographic Details
Published in:Nutrients 2023-06, Vol.15 (12), p.2742
Main Authors: Tuttis, Katiuska, Machado, Ana Rita Thomazela, Santos, Patrick Wellington da Silva, Antunes, Lusânia Maria Greggi
Format: Article
Language:English
Subjects:
Alfacalcidol
Androgens
Angiogenesis
Antibiotics
Antitumor activity
Apoptosis
Autophagy
BAX protein
Bioavailability
Biocompatibility
Calcifediol
Calciferol
Cancer therapies
Cell culture
Cell cycle
Cell growth
Cell viability
Clinical trials
Comet assay
Cytotoxicity
Damage detection
Deoxyribonucleic acid
DNA
DNA damage
Down-regulation
Ethylenediaminetetraacetic acid
Fluorescence
Functional foods & nutraceuticals
Gene expression
Health aspects
MAP kinase
Metastases
Metastasis
Oxidative stress
Plasma
Prostate cancer
Radiation
Radiotherapy
Signal transduction
Solvents
Sulforaphane
Tumor cells
Tumors
Vitamin D
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 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.
ISSN:2072-6643
2072-6643
DOI:10.3390/nu15122742