A high omega-3 fatty acid diet mitigates murine pancreatic precancer development.
BACKGROUND
Diets containing omega-3 (ω-3) fat have been associated with decreased tumor development in the colon, breast, and prostate. We assessed the effects of a diet rich in ω-3 fat on the development of pancreatic precancer in elastase (EL)-Kras transgenic mice and examined the effect of an ω-3 fatty acid on pancreatic cancer cells in vitro.


METHODS
Two cohorts of EL-Kras mice were fed a high ω-3 fat diet (23% menhaden oil) for 8 and 11 mo and compared with age-matched EL-Kras mice fed standard chow (5% fat). Pancreata from all mice were scored for incidence and frequency of precancerous lesions. Immunohistochemistry was performed for proliferating cell nuclear antigen (PCNA) to assess proliferative index in lesions of mice fed either a high ω-3 or standard diet. In vitro, the effect of the ω-3 fatty acid, docosahexaenoic acid (DHA), on two pancreatic cancer cell lines was assessed. Cancer cell proliferation was assessed with an MTT assay; cell cycle analysis was performed by flow cytometry; and apoptosis was assessed with annexin/PI staining.


RESULTS
The incidence, frequency, and proliferative index of pancreatic precancer in EL-Kras mice was reduced in mice fed a high ω-3 fat diet compared with mice fed a standard chow. In vitro, DHA treatment resulted in a concentration-dependent decrease in proliferation through both G1/G0 cell cycle arrest and induction of apoptosis.


CONCLUSIONS
A high ω-3 fat diet mitigates pancreatic precancer by inhibition of cellular proliferation through induction of cell cycle arrest and apoptosis.
Strouch
Matthew J
MJ
Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. p-grippo@northwestern.edu
Ding
Yongzeng
Y
Salabat
Mohammad R
MR
Melstrom
Laleh G
LG
Adrian
Kevin
K
Quinn
Christopher
C
Pelham
Carolyn
C
Rao
Sambasiva
S
Adrian
Thomas E
TE
Bentrem
David J
DJ
Grippo
Paul J
PJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000473:pathology / Q000517:prevention & control*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
D015525:Fatty Acids, Omega-3; D010196:Pancreatic Elastase; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)