Conjugated Linoleic Acid Reduction of Vascular Endothelial Growth Factor Expression in Murine Mammary Tumor Cells through Alteration of Prostaglandin E₂

Kim, Jung-Hyun,Hubbard, Neil E.,Lim, Debora,Erickson, Kent L. The Korean Society of Food Science and Nutrition 2006 Preventive Nutrition and Food Science Vol.11 No.1

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid that have been used to reduce the incidence, growth and metastasis of breast, colon, prostate and gastric cancer in animals. CLA could reduce tumor growth by altering angiogenesis; a process requiring associated angiogenic factors such as vascular endothelial growth factor (VEGF). In this study, we determined whether CLA could modulate the expression of VEGF in murine mammary tumor cells and adipocytes. The c9, t11-CLA isomer reduced VEGF transcripts and protein when mammary tumor cells were stimulated with PMA. That isomer also reduced VEGF expression in un stimulated mouse 3T3-L1 adipocytes. Since VEGF can be regulated by cyclooxygenase-2 (COX-2), we determined whether CLA could alter COX-2 enzyme expression and $PGE_2$ production. The c9, t11-CLA isomer reduced not only COX-2 enzyme expression but also $PGE_2$ production. Thus, c9, t11-CLA could modulate neovascularization by alteration of VEGF expression from mammary tumor cells and adipocytes by reducing COX-2 metabolites.

Conjugated Linoleic Acid Reduction of Vascular Endothelial Growth Factor Expression in Murine Mammary Tumor Cells through Alteration of Prostaglandin E2

Kent L. Erickson,Jung-Hyun Kim,Neil E. Hubbard,Debora Lim 한국식품영양과학회 2006 Preventive Nutrition and Food Science Vol.11 No.2

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid that have been used to reduce the incidence, growth and metastasis of breast, colon, prostate and gastric cancer in animals. CLA could reduce tumor growth by altering angiogenesis; a process requiring associated angiogenic factors such as vascular endothelial growth factor (VEGF). In this study, we determined whether CLA could modulate the expression of VEGF in murine mammary tumor cells and adipocytes. The c9, t11-CLA isomer reduced VEGF transcripts and protein when mammary tumor cells were stimulated with PMA. That isomer also reduced VEGF expression in unstimulated mouse 3T3-L1 adipocytes. Since VEGF can be regulated by cyclooxygenase-2 (COX-2), we determined whether CLA could alter COX-2 enzyme expression and PGE2 production. The c9, t11-CLA isomer reduced not only COX-2 enzyme expression but also PGE2 production. Thus, c9, t11-CLA could modulate neovascularization by alteration of VEGF expression from mammary tumor cells and adipocytes by reducing COX-2 metabolites.

Conjugated Linoleic Acid Reduction of Vascular Endothelial Growth Factor Expression in Murine Mammary Tumor Cells through Alteration of Prostaglandin E₂

Jung-Hyun Kim,Neil E. Hubbard,Debora Lim,Kent L. Erickson 한국식품영양과학회 2006 Preventive Nutrition and Food Science Vol.11 No.1

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid that have been used to reduce the incidence, growth and metastasis of breast, colon, prostate and gastric cancer in animals. CLA could reduce tumor growth by altering angiogenesis; a process requiring associated angiogenic factors such as vascular endothelial growth factor (VEGF). In this study, we determined whether CLA could modulate the expression of VEGF in murine mammary tumor cells and adipocytes. The c9, t11-CLA isomer reduced VEGF transcripts and protein when mammary tumor cells were stimulated with PMA. That isomer also reduced VEGF expression in unstimulated mouse 3T3-L1 adipocytes. Since VEGF can be regulated by cyclooxygenase-2 (COX-2), we determined whether CLA could alter COX-2 enzyme expression and PGE₂ production. The c9, t11-CLA isomer reduced not only COX-2 enzyme expression but also PGE₂ production. Thus, c9, t11-CLA could modulate neovascularization by alteration of VEGF expression from mammary tumor cells and adipocytes by reducing COX-2 metabolites.

Fatty Acid Modulation of Atherosclerosis by Peroxisome Proliferator - Activated Receptors

Kent L. Erickson,Neil E. Hubbard,Lynette M. Meinecke 한국식품영양과학회 2002 Preventive Nutrition and Food Science Vol.7 No.4

While atherosclerosis is a major killer, there is now concern that mortality from the disease will increase due to the rising incidence of type II diabetes. Because diet can potentially influence both diseases, it is important to elucidate the role of diet in the progression of atherosclerosis. In addition, the mechanisms involved in dietaryrelated alterations of the disease need to be defined to guide public health recommendations to reduce atherosclerosis incidence and limiting unwanted side effects. Since diet is thought to play a role in atherosclerosis even without added complications due to type II diabetes, reducing the incidence of that metabolic disease will not be enough. While evidence is increasing that high intake of carbohydrate can lead to type II diabetes and atherosclerosis, the preponderance of existing evidence indicates that intake of specific fats as a major dietary causal factor. It has recently been hypothesized that a dietary fat link to atherosclerosis may depend partly on the activity of a transcriptional regulator, the peroxisome proliferator activated receptors (PPAR). Thusfar, PPAR α, β/δ andγ, have been shown to play a major role in metabolism, inflammation, and cancer. Furthermore, PPAR may regulate specific processes associated with atherosclerosis such as triglyceride and low density lipoprotein (LDL) metabolism; the reverse cholesterol transport pathway; lipid accumulation within plaques; the local inflammatory response and plaque stability. Synthetic ligands for PPAR have been developed; however, natural ligands include specific fatty acids and their metabolites. Though the role of PPAR in atherosclerosis has been reported with respect to synthetic ligands, additional studies need to be done with established and possible natural ligands. In this review, we will focus on the relation of dietary fat to PPAR alteration of atherosclerosis.

Fatty Acid Modulation of Atherosclerosis by Peroxisome Proliferator- Activated Receptors

Erickson, Kent L.,Hubbard, Neil E.,Meinecke, Lynette M. The Korean Society of Food Science and Nutrition 2002 Preventive Nutrition and Food Science Vol.7 No.4

While atherosclerosis is a major killer, there is now concern that mortality from the disease will increase due to the rising incidence of type II diabetes. Because diet can potentially influence both diseases, it is important to elucidate the role of diet in the progression of atherosclerosis. In addition, the mechanisms involved in dietary-related alterations of the disease need to be defined to guide public health recommendations to reduce athero-sclerosis incidence and limiting unwanted side effects. Since diet is thought to play a role in atherosclerosis even without added complications due to type II diabetes, reducing the incidence of that metabolic disease will not be enough. While evidence is increasing that high intake of carbohydrate can lead to type II diabetes and atherosclerosis, the preponderance of existing evidence indicates that intake of specific fats as a major dietary causal factor. It has recently been hypothesized that a dietary fat link to atherosclerosis may depend partly on the activity of a transcriptional regulator, the peroxisome proliferator activated receptors (PPAR). Thusfar, PPAR $\alpha$, $\beta$/$\delta$ and ${\gamma}$, have been shown to play a major role in metabolism, inflammation, and cancer. Furthermore, PPAR may regulate specific processes associated with atherosclerosis such as triglyceride and low density lipoprotein (LDL) metabolism; the reverse cholesterol transport pathway; lipid accumulation within plaques; the local inflammatory response and plaque stability. Synthetic ligands for PPAR have been developed; however, natural ligands include specific fatty acids and their metabolites. Though the role of PPAR in atherosclerosis has been reported with respect to synthetic ligands, additional studies need to be done with established and possible natural ligands. In this review, we will focus on the relation of dietary fat to PPAR alteration of atherosclerosis.