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 Citations (Scopus)

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
StatePublished - Sep 12 2018

Fingerprint

Omega-3 Fatty Acids
omega-3 fatty acids
carcinogenesis
pancreatic neoplasms
Carcinogenesis
Fatty Acids
Diet
fatty acids
Pancreatic Neoplasms
diet
neoplasms
Neoplasms
mutation
penetrance
Exocrine Pancreas
Mutation
chemoprevention
counseling
Penetrance
Chemoprevention

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
Ding, Yongzeng ; Mullapudi, Bhargava ; Torres, Carolina ; Mascariñas, Emman ; Mancinelli, Georgina ; Diaz, Andrew M. ; McKinney, Ronald ; Barron, Morgan ; Schultz, Michelle ; Heiferman, Michael ; Wojtanek, Mireille ; Adrian, Kevin ; DeCant, Brian ; Musunuri, Sambasiva Rao ; Ouellette, Michel ; Tsao, Ming Sound ; Bentrem, David Jason ; Grippo, Paul J. / Omega-3 fatty acids prevent early pancreatic carcinogenesis via repression of the AKT pathway. In: Nutrients. 2018 ; Vol. 10, No. 9.
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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.",
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Ding, Y, Mullapudi, B, Torres, C, Mascariñas, E, Mancinelli, G, Diaz, AM, McKinney, R, Barron, M, Schultz, M, Heiferman, M, Wojtanek, M, Adrian, K, DeCant, B, Musunuri, SR, Ouellette, M, Tsao, MS, Bentrem, DJ & Grippo, PJ 2018, 'Omega-3 fatty acids prevent early pancreatic carcinogenesis via repression of the AKT pathway', Nutrients, vol. 10, no. 9, 1289. https://doi.org/10.3390/nu10091289

Omega-3 fatty acids prevent early pancreatic carcinogenesis via repression of the AKT pathway. / Ding, Yongzeng; Mullapudi, Bhargava; Torres, Carolina; Mascariñas, Emman; Mancinelli, Georgina; Diaz, Andrew M.; McKinney, Ronald; Barron, Morgan; Schultz, Michelle; Heiferman, Michael; Wojtanek, Mireille; Adrian, Kevin; DeCant, Brian; Musunuri, Sambasiva Rao; Ouellette, Michel; Tsao, Ming Sound; Bentrem, David Jason; Grippo, Paul J.

In: Nutrients, Vol. 10, No. 9, 1289, 12.09.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Omega-3 fatty acids prevent early pancreatic carcinogenesis via repression of the AKT pathway

AU - Ding, Yongzeng

AU - Mullapudi, Bhargava

AU - Torres, Carolina

AU - Mascariñas, Emman

AU - Mancinelli, Georgina

AU - Diaz, Andrew M.

AU - McKinney, Ronald

AU - Barron, Morgan

AU - Schultz, Michelle

AU - Heiferman, Michael

AU - Wojtanek, Mireille

AU - Adrian, Kevin

AU - DeCant, Brian

AU - Musunuri, Sambasiva Rao

AU - Ouellette, Michel

AU - Tsao, Ming Sound

AU - Bentrem, David Jason

AU - Grippo, Paul J.

PY - 2018/9/12

Y1 - 2018/9/12

N2 - 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.

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KW - Neoplastic disease

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KW - Polyunsaturated fatty acids

KW - Proliferation

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Ding Y, Mullapudi B, Torres C, Mascariñas E, Mancinelli G, Diaz AM et al. Omega-3 fatty acids prevent early pancreatic carcinogenesis via repression of the AKT pathway. Nutrients. 2018 Sep 12;10(9). 1289. https://doi.org/10.3390/nu10091289