Omega-3 fatty acids prevent early pancreatic carcinogenesis via repression of the AKT pathway

Yongzeng Ding, Bhargava Mullapudi, Carolina Torres*, Emman Mascariñas, Georgina Mancinelli, Andrew M. Diaz, Ronald McKinney, Morgan Barron, Michelle Schultz, Michael Heiferman, Mireille Wojtanek, Kevin Adrian, Brian DeCant, Sambasiva Rao Musunuri, Michel Ouellette, Ming Sound Tsao, David Jason Bentrem, Paul J. Grippo

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Pancreatic cancer remains a daunting foe despite a vast number of accumulating molecular analyses regarding the mutation and expression status of a variety of genes. Indeed, most pancreatic cancer cases uniformly present with a mutation in the KRAS allele leading to enhanced RAS activation. Yet our understanding of the many epigenetic/environmental factors contributing to disease incidence and progression is waning. Epidemiologic data suggest that diet may be a key factor in pancreatic cancer development and potentially a means of chemoprevention at earlier stages. While diets high in ω3 fatty acids are typically associated with tumor suppression, diets high in ω6 fatty acids have been linked to increased tumor development. Thus, to better understand the contribution of these polyunsaturated fatty acids to pancreatic carcinogenesis, we modeled early stage disease by targeting mutant KRAS to the exocrine pancreas and administered diets rich in these fatty acids to assess tumor formation and altered cell-signaling pathways. We discovered that, consistent with previous reports, the ω3-enriched diet led to reduced lesion penetrance via repression of proliferation associated with reduced phosphorylated AKT (pAKT), whereas the ω6-enriched diet accelerated tumor formation. These data provide a plausible mechanism underlying previously observed effects of fatty acids and suggest that administration of ω3 fatty acids can reduce the pro-survival, pro-growth functions of pAKT. Indeed, counseling subjects at risk to increase their intake of foods containing higher amounts of ω3 fatty acids could aid in the prevention of pancreatic cancer.

Original languageEnglish (US)
Article number1289
JournalNutrients
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 12 2018

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Keywords

  • Chemoprevention
  • Neoplastic disease
  • Pancreatic cancer
  • Polyunsaturated fatty acids
  • Proliferation

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

Ding, Y., Mullapudi, B., Torres, C., Mascariñas, E., Mancinelli, G., Diaz, A. M., ... Grippo, P. J. (2018). Omega-3 fatty acids prevent early pancreatic carcinogenesis via repression of the AKT pathway. Nutrients, 10(9), [1289]. https://doi.org/10.3390/nu10091289