Effects of Polyunsaturated Fatty Acids and Selenoneine on Growth and Lipidomic Profiles in Patient-Derived Prostate Cancer Organoids
- 1Centre de Recherche CHU de Québec-Université Laval
Abstract
Prostate cancer (PCa) is the second most frequent cancer in men and represents a major public health issue worldwide. To complement current therapeutic approaches, our work aims to understand the impact of nutritional interventions on PCa evolution. Recent studies showed that supplementation with omega-3 fatty acids reduces tumour growth in PCa mouse models. Several beneficial effects were observed, particularly on the gut microbiome, suggesting indirect effects on tumours, and whether these fatty acids have a direct molecular impact on the prostate remains elusive. Here, we hypothesized that the prostate directly takes up dietary fatty acids to reprogram metabolism, which could contribute to the beneficial effects on cancer treatment. To test this hypothesis, five series of patient-derived organoids (PDOs), with paired lines originating from normal and tumour samples, were treated with omega-3 and omega-6 fatty acids. While heterogeneity was observed in growth capacities of PDO lines, omega-3 supplementation overall decreased PDO growth, with a stronger decrease in PCa lines. This effect was stronger when co-treated with selenoneine, a nutrient enriched in some marine foods with high omega-3 content. Lipidomic experiments were then performed, revealing that PDOs can take up fatty acids, both omega-3 and omega-6. Furthermore, PDOs could metabolize omega-3 fatty acids into downstream metabolites, even if high inter-patient heterogeneity was observed. Altogether, this study, using PDOs as a working model to study the human prostate, provides a better understanding of the molecular impacts of fatty acid supplementation on prostate and PCa biology for the development of future nutritional interventions.
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BibTeX
@misc{sylla2026effects,
title = {{Effects of Polyunsaturated Fatty Acids and Selenoneine on Growth and Lipidomic Profiles in Patient-Derived Prostate Cancer Organoids}},
author = {M. S. Sylla and C. Jobin and L. Berthiaume and L. Leclair and G. Lachance and K. Robitaille and C. Menard and C. Atallah and F. Pouliot and P. Ayotte and Y. Fradet and V. Fradet and E. Audet-Walsh},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749239},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749239v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Effects of Polyunsaturated Fatty Acids and Selenoneine on Growth and Lipidomic Profiles in Patient-Derived Prostate Cancer Organoids
AU - M. S. Sylla
AU - C. Jobin
AU - L. Berthiaume
AU - L. Leclair
AU - G. Lachance
AU - K. Robitaille
AU - C. Menard
AU - C. Atallah
AU - F. Pouliot
AU - P. Ayotte
AU - Y. Fradet
AU - V. Fradet
AU - E. Audet-Walsh
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749239
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749239v1
AB - Prostate cancer (PCa) is the second most frequent cancer in men and represents a major public health issue worldwide. To complement current therapeutic approaches, our work aims to understand the impact of nutritional interventions on PCa evolution. Recent studies showed that supplementation with omega-3 fatty acids reduces tumour growth in PCa mouse models. Several beneficial effects were observed, particularly on the gut microbiome, suggesting indirect effects on tumours, and whether these fatty acids have a direct molecular impact on the prostate remains elusive. Here, we hypothesized that the prostate directly takes up dietary fatty acids to reprogram metabolism, which could contribute to the beneficial effects on cancer treatment. To test this hypothesis, five series of patient-derived organoids (PDOs), with paired lines originating from normal and tumour samples, were treated with omega-3 and omega-6 fatty acids. While heterogeneity was observed in growth capacities of PDO lines, omega-3 supplementation overall decreased PDO growth, with a stronger decrease in PCa lines. This effect was stronger when co-treated with selenoneine, a nutrient enriched in some marine foods with high omega-3 content. Lipidomic experiments were then performed, revealing that PDOs can take up fatty acids, both omega-3 and omega-6. Furthermore, PDOs could metabolize omega-3 fatty acids into downstream metabolites, even if high inter-patient heterogeneity was observed. Altogether, this study, using PDOs as a working model to study the human prostate, provides a better understanding of the molecular impacts of fatty acid supplementation on prostate and PCa biology for the development of future nutritional interventions.
ER -