chung s. park animal science department north dakota state university november, 2012 canola oil and...
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Chung S. ParkAnimal Science Department
North Dakota State UniversityNovember, 2012
Canola Oil and Breast Cancer Research Projects
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Topics
1. Maternal lipotropes (methyl nutrients) diet and mammary cancer-Chung Park
2. Maternal canola oil supplementation and mammary cancer-Lawrence Mabasa
3. Update of Lipocan project progress-Lawrence Mabasa
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Maternal lipotrope (methyl) and mammary carcinogenesis in offspring
LIPOCAN= Lipotrope + Canola Oil
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Our previous work
Over the past 22 years, our laboratory has studied link between lipotrope and mammary cancer
• Lipotropes can alter the expression of genes that are associated with cell growth and metabolism in the mammary glands
• Manipulation of dietary lipotropes can affect susceptibility of virgin female rats to mammary cancer
(Park et al., 2010. Advances in Medicine and Biology, Vol.12)
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Lipotropes (methyl nutrients)
Lipotropes are methyl (-CH3) group containing amino acid and vitamins (methionine, choline, folate, and vitamin B12)
Play major role in one-carbon metabolism (DNA methylation and synthesis), which is involved in epigenetic imprinting
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Epigenetics: imprint
Permanent alterations in gene expression and metabolism that occur during early fetal development
Epigenetic modifications are inheritable and affected by environment, notably nutrition/diet
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“Things written in pen you can’t change. That’s DNA. Things written in pencil you can. That’s epigenetics.”-Danielle Reed
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Maternal nutrition & offspring health
Maternal nutrition may lead to metabolic imprinting (biological memory) which can be passed on to offspring
Prenatal and early postnatal
nutrition
Metabolic imprinting (program)
Lifetime susceptibility to chronic disease
in offspring
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Maternal nutrition and breast cancer
More complete and full mammary development during full-term pregnancy is closely associated with a long-term reduction of mammary cancer
Maternal diet/nutrition
Epigenetic modifications
(moms, offspring)
Mammary gland
development Breast
cancer risk
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“You are what your mother ate”
Your mother’s diet during pregnancy can cause critical changes
that stick with you into adulthood
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Methyl nutrients and cancer studies
Most studies have been concerned with the effects of methyl deprivation upon carcinogenesis
However, dietary methyl deficiency has minimum relevancy because normal human diets are unlikely to be deficient
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Methyl nutrients and cancer studies
Studies address the effect of individual methyl nutrients (e.g., folic acid) on breast cancer
However, there have been no studies which address the interplay among all four methyl nutrients on reduction of breast cancer
Supplementation – novel concept
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Maternal diet with3x methyl nutrients
Yellow mouse
Reduced lifespan High risk of
obesity, diabetes, and cancer
Prolonged lifespan Lower risk of
obesity, diabetes, and cancer
Agouti mouse
Cooney et al. (2002) J Nutr.
Mom Offspring
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Hypothesis
“In Utero exposure to lipotropes decreases mammary carcinogenesis in offspring”
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Funded by Department of Defense-Medical Research Program
Findings
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Mammary carcinogenesis in offspring
Item Control Methyl-diet
Tumor incidence (%) 100 53.3* (47% ↓)
Latency period (weeks) 7.93 ± 0.32 11.27 ± 0.85* (42% ↑)
Tumor multiplicity (# of tumors/rat) 2.93 ± 0.21 1.20 ± 0.23* (59% ↓)
(* P<0.05)
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Summary
In utero exposure to lipotrope supplementation:
• Significantly reduced chemically-induced mammary carcinogenesis in offspring
• The first experimental evidence linking maternal lipotropic diet (all four methyl nutrients) to reduced mammary carcinogenesis in offspring• Published in Carcinogenesis June 2012
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“Lipotropes and mammary carcinogenesis”
Carcinogenesis 33:1106-1112 (2012)
Research in Veterinary Science 93:259-263 (2012)
In Advances in Medicine and Biology Vol.12:133-139 (2010)
In Vitro Cell Dev Biol-Anim 44:268-272 (2008)
Recent publications
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Current and future studies
?IN
Prenatal exposure to lipotropes
Reduction of mammary
carcinogenesis in offspring
OUT
Black box
Currently funded by National Institutes of Health (2012-14)
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Support
Lipotrope and mammary cancer
• NIH-National Cancer Institute
1998, 2002, 2012 (active)
• DOD-Breast Cancer Research Program
• 1994, 2009
• American Institute for Cancer Research
2003
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Maternal canola oil supplementation and mammary
cancer risk in offspring
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Objective
The objective of the study was to investigate the role of maternal dietary canola oil on the susceptibility of female offspring to mammary carcinogenesis
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Protocol
Pregnant rats were fed either of the following diets:
• Control diet (containing 10% soybean oil)
• Canola oil diet (10% canola oil)
After weaning, offspring were fed the control diet and then injected with NMU (which is a chemical carcinogen) to induce mammary cancer
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Results
Mammary carcinogenesis data in offspring
Item Control Canola P
Tumor incidence (%) 8773
( 16%)
Latency period
(weeks)11.08±0.90
11.90±0.9
60.71
Tumor multiplicity/no. 1.93±0.32
1.02±0.250.04
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Results
0100020003000400050006000700080009000
Control
Weeks after NMU injection
Tu
mo
r vo
lum
e (
mm
3)
* * * * *
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Summary
Maternal canola oil diet reduced overall mammary carcinogenesis in offspring
Manuscript of this work is currently undergoing revision in the Journal of Nutrition
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Lipotropes plus canola oil (lipocan) projects
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Rationale
Lipotropes
Canola oil
Supplementation
Anti-breast cancer effect
+Synergistic
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Background
In 2011, we received support from the NCGA to study the effect of lipocan (lipotropes plus canola oil) on mammary cancer risk
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Strategy
To complete the US patent application:
• Phase I: data gathering on the anticancer effect of lipocan
• Phase II: studying the mechanism, how lipocan reduces mammary cancer risk
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Progress
Currently two independent projects are ongoing:
• Experiment 1 deals with the effect of lipocan on virgin rats
• Experiment 2 involves the role of maternal lipocan on the risk of offspring to cancer
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Time line
Physical evidence, and data collection
Mechanism and patent
application
Animal trials (experiment 1&2)
Some tissue sample assays
2011 2012 2013 2014
PHASE I PHASE II
Animal trials (experiment 2)
Tissue sample assays
Writing up reports
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Implications
Results may be useful in development of a nutraceutical product (lipocan) to reduce long term breast cancer risk in humans
US patent royalties
• 30% Inventor: NCGA
• 30-50% NDSU Animal Sciences Department
• 20-35% NDSU Research Foundation
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Support and Personnel
Northern Canola Growers Association
L. Mabasa K. Cho S. Bae M. Walters Dr. Park
Acknowledgment