Effects of Docosahexaenoic Acid on Prostate Cancer
Abstract
1. Introduction
2. Overview of Molecular Aspects, Metabolism, and Sources
3. DHA Levels in Normal and PCa Cells: Evidence for a Tumor Suppressor?
4. Epidemiologic Findings on DHA Association with PCa Risk
5. Experimental Evidence on DHA’s Effect Against PCa
5.1. Androgen Signaling
5.2. Nuclear Receptors
5.3. Metabolism
5.4. Modulation of Cell Death
5.5. Modulation of Prostate Tumor Microenvironment
5.6. Combination of DHA with Other Therapies
GENE | DHA EFFECT | MODEL (S) | FUNCTION | REFERENCE |
---|---|---|---|---|
AKT1 | ↓ | LNCaP, DU145 | 1, 2, 4 | [178] |
AR | ↓ | DU145 | 1–6 | [86] |
ATF3 | ↑ | PC3 | 2 | [22] |
BAX | ↑ | DU145 | 2 | [157] |
CASP1 | ↑ | DU145 | 2 | [157] |
CASP3 | ↑ | DU145 | 2 | [157] |
CASP9 | ↑ | DU145 | 2 | [157] |
CCNA2 | ↓ | PC3 | 1 | [22] |
CCND2 | ↑ | PC3 | 1 | [22] |
CIDEA | ↑ | DU145 | 2 | [157] |
DRG-1 | ↓ | LNCaP | 6 | [86] |
ERRFI1 | ↑ | PNT1A | 1, 4, 5 | [9] |
FADD | ↓ | LNCaP, DU145 | 2 | [178] |
FASN | ↓ | PC3 | 3 | [22] |
FKBP51 | ↓ | LNCaP cells | 1, 3, 5 | [86] |
FOS | ↓ | PNT1A, 22Rv1 | 1 | [9] |
HDAC5 | ↑ | 22Rv1 | 1, 3 | [9] |
IL6 | ↑ | PC3 | 3 | [22] |
IL10 | ↑ | PC3 | 3 | [22] |
KLK3 | ↓ | LNCaP | 7 | [86] |
LTA | ↑ | DU145 | 2 | [157] |
ODC | ↓ | LNCaP cells | 2, 5 | [86] |
PPARG | ↑ | PNT1A | 1, 4 | [9] |
PPARGC1A | ↓ | PNT1A, PC3 | 1, 4 | [9] |
PPARGC1B | ↑ | 22Rv1 | 1, 4 | [9] |
MAX | ↓ | LNCaP, DU145 | 1, 2 | [178] |
MAP2K4 | ↓ | LNCaP, DU145 | 1, 2, 6 | [178] |
NKX3.1 | ↓ | LNCaP | 1, 6 | [86] |
NR0B1 | ↑↓ | PNT1A, 22Rv1, PC3 | 4, 5, 7 | [9] |
PTGS2 | ↑ | PC3 | 3 | [22] |
RIPK1 | ↓ | LNCaP, DU145 | 2 | [178] |
RORA | ↑ | 22Rv1 | 4, 5 | [9] |
TNFRSF11A | ↓↑ | LNCaP, DU145 | 2, 3, 6 | [178] |
TMPRSS2 | ↓ | LNCaP | 1 | [86] |
TP53 | ↑ | DU145 | 2, 6 | [157] |
TRAF3 | ↓ | LNCaP, DU145 | 2, 3 | [178] |
WAF/CIP1 | ↑ | PC3 | 1 | [22] |
6. Conclusions, Limitations, and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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MECHANISM | MAIN GAPS FOUND IN THE LITERATURE | POTENTIAL TRANSLATIONAL APPROACH |
---|---|---|
Androgen signaling | In vivo studies; in vitro combination with ARSIs simultaneously or considering DHA pre-incubation; lack of study using AR genetic editing for validation | Combination of DHA intake with ARSIs currently available |
Nuclear Receptors | Determination of whether PPARs are protective or promote PCa; in vivo and in vitro studies with DHA combined with PPARs inhibitors; association with androgenic background | Combination of DHA intake with PPAR inhibitors in patients stratified according to PTEN expression; combination of DHA with drugs that regulate GR. |
Metabolism | Combination with lipogenesis and cholesterol biosynthesis inhibitors in vivo and in vitro; lack of carbon-labeled experiments to evaluate the metabolic flux | Synergistic effect of DHA intake with lipid metabolism inhibitors under clinical trial |
Cell Death | In vivo assays; lacks assessment of combination either in vitro or in vivo with cell death inhibitors with proper controls | Synergistic effect of DHA intake with cell death inducers under clinical trial, simultaneously or as pretreatment |
TME | Co-culture assays to validate hypothesis; functional assays ex vivo to validate lymphoid and myeloid function; specific assessment of DHA in COLD and HOT TME | Stratification of patients according to inflammatory infiltrates; combination of DHA intake with the current therapy |
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Tamarindo, G.H.; Amaro, G.M.; da Silva, A.D.T.; Góes, R.M. Effects of Docosahexaenoic Acid on Prostate Cancer. J. Xenobiot. 2025, 15, 111. https://doi.org/10.3390/jox15040111
Tamarindo GH, Amaro GM, da Silva ADT, Góes RM. Effects of Docosahexaenoic Acid on Prostate Cancer. Journal of Xenobiotics. 2025; 15(4):111. https://doi.org/10.3390/jox15040111
Chicago/Turabian StyleTamarindo, Guilherme Henrique, Gustavo Matheus Amaro, Alana Della Torre da Silva, and Rejane Maira Góes. 2025. "Effects of Docosahexaenoic Acid on Prostate Cancer" Journal of Xenobiotics 15, no. 4: 111. https://doi.org/10.3390/jox15040111
APA StyleTamarindo, G. H., Amaro, G. M., da Silva, A. D. T., & Góes, R. M. (2025). Effects of Docosahexaenoic Acid on Prostate Cancer. Journal of Xenobiotics, 15(4), 111. https://doi.org/10.3390/jox15040111