Dietary Walnut Suppression of Colorectal Cancer in mice: mediation by miRNA patterns and fatty acid incorporation Michael A. Tsoukas, Byung-Joon Ko, Theodore R. Witte, Fadime Dincer, W. Elaine Hardman, Christos S. Mantzoros PII: DOI: Reference:
S0955-2863(15)00070-4 doi: 10.1016/j.jnutbio.2015.02.009 JNB 7331
To appear in:
The Journal of Nutritional Biochemistry
Received date: Revised date: Accepted date:
17 June 2014 29 January 2015 11 February 2015
Please cite this article as: Tsoukas Michael A., Ko Byung-Joon, Witte Theodore R., Dincer Fadime, Hardman W. Elaine, Mantzoros Christos S., Dietary Walnut Suppression of Colorectal Cancer in mice: mediation by miRNA patterns and fatty acid incorporation, The Journal of Nutritional Biochemistry (2015), doi: 10.1016/j.jnutbio.2015.02.009
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Research article;
Dietary Walnut Suppression of Colorectal Cancer in mice:
RI P
T
mediation by miRNA patterns and fatty acid incorporation Michael A. Tsoukas1,2, Byung-Joon Ko1, Theodore R. Witte3, Fadime Dincer1,
SC
W. Elaine Hardman3, Christos S. Mantzoros1,2 1
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center,
NU
Harvard Medical School, Boston, MA 2
Section of Endocrinology, Boston VA Healthcare system, Boston, MA
MA
3
ED
Department of Biochemistry and Microbiology, Marshall University School of Medicine, Huntington, WV
Corresponding Author:
PT
Michael A. Tsoukas, MD [email protected]
CE
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
AC
Tel.: + 1 617 667 8632; fax: + 1 617 667 8634
Word Count: 5,709; Number of References: 71; Number of Tables/Figures: 7 Running title: Walnut suppression of colon cancer by miRNA mediation Conflicts of interest: The authors have no conflicts of interest to disclose.
Funding: This study was supported from a grant by the American Institute for Cancer Research (276688) and the California Walnut Commission. The content is solely the responsibility of the authors and does not necessarily represent the official views of the American Institute for Cancer Research and the California Walnut Commission; sponsors had no input on interpretation or reporting of findings.
ACCEPTED MANUSCRIPT Abstract Colorectal cancer, unlike many other malignancies, may be preventable. Recent studies have demonstrated an inverse association between nut consumption and incidence of colon cancer,
RI P
T
however the underlying mechanisms are not fully understood. An emerging concept suggests that micro-ribonucleic acids (miRNA) may help explain the relationship between walnut
SC
consumption and decreased colorectal neoplasia risk.
Seven days after HT-29 colon cancer cell injection, mice were randomized to either control or walnut diets for 25 days of diet treatment. Thirty samples of tumor and of omental adipose were
NU
analyzed to determine changes in lipid composition in each dietary group. In the tumors of the walnut-containing diet, we found significant increases in -linolenic, eicosapentaenoic,
MA
docosahexaenoic, and total omega-3 acids, and a decrease in arachidonic acid, as compared to the control diet. Final tumor size measured at sacrifice was negatively associated with percentage
ED
of total omega-3 fatty acid composition (r=-0.641,p=0.001). MicroRNA expression analysis of colorectal tumor tissue revealed decreased expression of miRNA 1903, 467c, and 3068 (p
S0955-2863(15)00070-4 doi: 10.1016/j.jnutbio.2015.02.009 JNB 7331
To appear in:
The Journal of Nutritional Biochemistry
Received date: Revised date: Accepted date:
17 June 2014 29 January 2015 11 February 2015
Please cite this article as: Tsoukas Michael A., Ko Byung-Joon, Witte Theodore R., Dincer Fadime, Hardman W. Elaine, Mantzoros Christos S., Dietary Walnut Suppression of Colorectal Cancer in mice: mediation by miRNA patterns and fatty acid incorporation, The Journal of Nutritional Biochemistry (2015), doi: 10.1016/j.jnutbio.2015.02.009
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Research article;
Dietary Walnut Suppression of Colorectal Cancer in mice:
RI P
T
mediation by miRNA patterns and fatty acid incorporation Michael A. Tsoukas1,2, Byung-Joon Ko1, Theodore R. Witte3, Fadime Dincer1,
SC
W. Elaine Hardman3, Christos S. Mantzoros1,2 1
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center,
NU
Harvard Medical School, Boston, MA 2
Section of Endocrinology, Boston VA Healthcare system, Boston, MA
MA
3
ED
Department of Biochemistry and Microbiology, Marshall University School of Medicine, Huntington, WV
Corresponding Author:
PT
Michael A. Tsoukas, MD [email protected]
CE
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
AC
Tel.: + 1 617 667 8632; fax: + 1 617 667 8634
Word Count: 5,709; Number of References: 71; Number of Tables/Figures: 7 Running title: Walnut suppression of colon cancer by miRNA mediation Conflicts of interest: The authors have no conflicts of interest to disclose.
Funding: This study was supported from a grant by the American Institute for Cancer Research (276688) and the California Walnut Commission. The content is solely the responsibility of the authors and does not necessarily represent the official views of the American Institute for Cancer Research and the California Walnut Commission; sponsors had no input on interpretation or reporting of findings.
ACCEPTED MANUSCRIPT Abstract Colorectal cancer, unlike many other malignancies, may be preventable. Recent studies have demonstrated an inverse association between nut consumption and incidence of colon cancer,
RI P
T
however the underlying mechanisms are not fully understood. An emerging concept suggests that micro-ribonucleic acids (miRNA) may help explain the relationship between walnut
SC
consumption and decreased colorectal neoplasia risk.
Seven days after HT-29 colon cancer cell injection, mice were randomized to either control or walnut diets for 25 days of diet treatment. Thirty samples of tumor and of omental adipose were
NU
analyzed to determine changes in lipid composition in each dietary group. In the tumors of the walnut-containing diet, we found significant increases in -linolenic, eicosapentaenoic,
MA
docosahexaenoic, and total omega-3 acids, and a decrease in arachidonic acid, as compared to the control diet. Final tumor size measured at sacrifice was negatively associated with percentage
ED
of total omega-3 fatty acid composition (r=-0.641,p=0.001). MicroRNA expression analysis of colorectal tumor tissue revealed decreased expression of miRNA 1903, 467c, and 3068 (p
