Influence of Caloric Intake on Experimental Carcinogenesis: A Review

Kritchevsky, David; Klurfeld, David M.

doi:10.1007/978-1-4613-1835-4_7

Cited by 31 publications

(18 citation statements)

References 11 publications

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“…Thus, by pharmacologically activating some of the intracellular control systems physiologically activated by nutrient deprivation, metformin acts as an inhibitor of proliferation. It is a classic experimental observation that severe dietary restriction protects rodents from a variety of carcinogenic influences (12). There is evidence (reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

Metformin Is an AMP Kinase–Dependent Growth Inhibitor for Breast Cancer Cells

Zakikhani¹,

et al. 2006

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Recent population studies provide clues that the use of metformin may be associated with reduced incidence and improved prognosis of certain cancers. This drug is widely used in the treatment of type 2 diabetes, where it is often referred to as an ''insulin sensitizer'' because it not only lowers blood glucose but also reduces the hyperinsulinemia associated with insulin resistance. As insulin and insulin-like growth factors stimulate proliferation of many normal and transformed cell types, agents that facilitate signaling through these receptors would be expected to enhance proliferation. We show here that metformin acts as a growth inhibitor rather than an insulin sensitizer for epithelial cells. Breast cancer cells can be protected against metformin-induced growth inhibition by small interfering RNA against AMP kinase. This shows that AMP kinase pathway activation by metformin, recently shown to be necessary for metformin inhibition of gluconeogenesis in hepatocytes, is also involved in metformininduced growth inhibition of epithelial cells. The growth inhibition was associated with decreased mammalian target of rapamycin and S6 kinase activation and a general decrease in mRNA translation. These results provide evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent population studies and justify further work to explore potential roles for activators of AMP kinase in cancer prevention and treatment.

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Section: Discussionmentioning

confidence: 99%

Metformin Is an AMP Kinase–Dependent Growth Inhibitor for Breast Cancer Cells

Zakikhani¹,

et al. 2006

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“…Mice kept under hypoxic conditions initially lost weight, but after a week gained weight at the same rate as normoxic mice. Experimental weight loss typically has a suppressive effect on carcinogenesis and tumor progression, but we cannot be sure that hypoxia induced weight loss might not have different effects, although this seems unlikely (33). Alveolar hypoxia did not increase tumor multiplicity in these models and indeed resulted in a statistically significant decrease in tumor multiplicity in the MCA/BHT model, as well as in intermittent hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Alveolar Hypoxia Promotes Murine Lung Tumor Growth through a VEGFR-2/EGFR-Dependent Mechanism

Karoor

Merrick

et al. 2012

Cancer Prevention Research

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Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for the development of lung cancer, the mechanisms for which are incompletely understood. We hypothesized that the hypoxic pulmonary microenvironment present in COPD would augment lung carcinogenesis. Mice were subjected to chemical carcinogenesis protocols and placed in either hypoxia or normoxia. Mice exposed to chronic hypoxia developed tumors with increased volume compared to normoxic controls. Both lungs and tumors from hypoxic mice showed a preferential stabilization of HIF-2α and increased expression of VEGF-A, FGF2 and their receptors as well as other survival, proliferation and angiogenic signaling pathways regulated by HIF-2α. We demonstrated that tumors arising in hypoxic animals have increased sensitivity to VEGFR-2/EGFR inhibition, as chemoprevention with vandetanib showed markedly increased activity in hypoxic mice. These studies demonstrate that lung tumors arising in an hypoxic microenvironment express increased growth, angiogenic and survival signaling that could contribute to the increased lung cancer risk in COPD. Furthermore, the differential sensitivity of tumors arising in hypoxia to VEGFR-2/EGFR inhibition suggests that the altered signaling present in tumors arising in hypoxic lung might be therapeutically exploited in patients with underlying COPD.

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“…The cancer-inhibitory activity of weight loss by calorie restriction and/or exercise has been well documented in many animal models, including the skin carcinogenic model (5). A relationship between reduced dietary energy intake and decreased tumor rates has been established in rodents (6).…”

Section: Introductionmentioning

confidence: 99%

Weight Loss via Exercise with Controlled Dietary Intake May Affect Phospholipid Profile for Cancer Prevention in Murine Skin Tissues

Ouyang

Jiang

Doan

et al. 2010

Cancer Prevention Research

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Exercise has been linked to a reduced cancer risk in animal models. However, the underlying mechanisms are unclear. This study assessed the effect of exercise with dietary consideration on the phospholipid profile in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin tissues. CD-1 mice were randomly assigned to one of the three groups: ad libitum-fed sedentary control; ad libitum-fed treadmill exercise at 13.4 m/min for 60 min/d, 5 d/wk (Ex+AL); and treadmill-exercised but pair-fed with the same amount as the control (Ex+PF). After 14 weeks, Ex+PF but not Ex+AL mice showed ∼25% decrease in both body weight and body fat when compared with the controls. Of the total 338 phospholipids determined by electrospray ionization-tandem mass spectrometry, 57 were significantly changed, and 25 species could distinguish effects of exercise and diet treatments in a stepwise discriminant analysis. A 36% to 75% decrease of phosphatidylinositol (PI) levels in Ex+PF mice occurred along with a significant reduction of PI 3-kinase in TPA-induced skin epidermis, as measured by both Western blotting and immunohistochemistry. In addition, ∼2-fold increase of the long-chain polyunsaturated fatty acids, docosahexaenoic and docosapentaenoic acids, in phosphatidylcholines, phosphatidylethanolamines, and lysophosphatidylethanolamines was observed in the Ex+PF group. Microarray analysis indicated that the expression of fatty acid elongase-1 increased. Taken together, these data indicate that exercise with controlled dietary intake, but not exercise alone, significantly reduced body weight and body fat as well as modified the phospholipid profile, which may contribute to cancer prevention by reducing TPAinduced PI 3-kinase and by enhancing ω-3 fatty acid elongation. Cancer Prev Res; 3(4); 466-77. ©2010 AACR.

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Influence of Caloric Intake on Experimental Carcinogenesis: A Review

Cited by 31 publications

References 11 publications

Metformin Is an AMP Kinase–Dependent Growth Inhibitor for Breast Cancer Cells

Metformin Is an AMP Kinase–Dependent Growth Inhibitor for Breast Cancer Cells

Alveolar Hypoxia Promotes Murine Lung Tumor Growth through a VEGFR-2/EGFR-Dependent Mechanism

Weight Loss via Exercise with Controlled Dietary Intake May Affect Phospholipid Profile for Cancer Prevention in Murine Skin Tissues

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