High fat, refined sugar diet increases IGF1

Growth Horm IGF Res. 2010 Feb;20(1):55-62. Epub 2009 Oct 22.

Pomegranate extract induces apoptosis in human prostate cancer cells by modulation of the IGF-IGFBP axis.

Koyama S, Cobb LJ, Mehta HH, Seeram NP, Heber D, Pantuck AJ, Cohen P.

Division of Pediatric Endocrinology, Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles, USA.

Abstract

The IGF axis is critical for the regulation of apoptosis in many human cancer cell lines. Recently, potent anti-tumorigenic effects of pomegranate juice and extracts have been reported. Consequently, pomegranate has potential not only as a treatment but also as a preventative measure against certain types of cancer, including prostate. In this study, we investigated the relationship between pomegranate-induced apoptosis in human prostate cancer cells and the IGF/IGFBP system. Treatment of LAPC4 prostate cancer cells with 10microg/ml POMx, a highly potent pomegranate extract prepared from skin and arils minus seeds and standardized to ellagitannin content (37% punicalagins by HPLC), resulted in inhibition of cell proliferation and induction of apoptosis. Interestingly, co-treatment with POMx and IGFBP-3 revealed synergistic stimulation of apoptosis and additive inhibition of cell growth. Western blot analysis revealed that treatment with POMx or POMx/IGFBP-3 combination resulted in increased JNK phosphorylation, and decreased Akt and mTOR activation, consistent with a growth inhibitory, pro-apoptotic function. We also investigated the relationship between IGF-1 and pomegranate-induced apoptosis in 22RV1 prostate cancer cells. Co-treatment with 100ng/ml IGF-1 completely blocked apoptosis induction by POMx. In contrast, IGF-I failed to inhibit POMx-induced apoptosis in R(-) cells, suggesting the importance of IGF-IR. POMx-treatment decreased Igf1 mRNA expression in a dose-dependent manner indicating that its actions also involve tumor-specific suppression of IGF-1. These studies revealed novel interactions between the IGF system and pomegranate-induced apoptosis.

Copyright 2009 Elsevier Ltd. All rights reserved

Health effects of vegan diets

Health effects of vegan diets

Winston J Craig

ABSTRACT

Recently, vegetarian diets have experienced an increase in popularity.

Avegetarian diet is associated with many health benefits because

of its higher content of fiber, folic acid, vitamins C and E, potassium,

magnesium, and many phytochemicals and a fat content that is more

unsaturated. Compared with other vegetarian diets, vegan diets tend

to contain less saturated fat and cholesterol and more dietary fiber.

Vegans tend to be thinner, have lower serum cholesterol, and lower

blood pressure, reducing their risk of heart disease. However, eliminating

all animal products from the diet increases the risk of certain

nutritional deficiencies. Micronutrients of special concern for the

vegan include vitamins B-12 and D, calcium, and long-chain n–3

(omega-3) fatty acids. Unless vegans regularly consume foods that

are fortified with these nutrients, appropriate supplements should be

consumed. In some cases, iron and zinc status of vegans may also be

of concern because of the limited bioavailability of these

minerals.

Am J Clin Nutr

2009;89(suppl):1627S–33S.

Full free article in PDF http://www.ajcn.org/content/89/5/1627S.full.pdf+html

Actions of IGF-1 in Relation to Cancer

IGF-1 exerts powerful effects on each of the key stages of cancer development and behaviour: cellular proliferation and apoptosis, angiogenesis and metastasis, and more recently, development of resistance to chemotherapeutic agents.^[2,3] It is a potent proliferative agent affecting almost every cell type, an effect predominantly, although not exclusively, mediated via the mitogen-activated protein (MAP) kinase signalling pathway. In addition to these proliferative actions, IGF-1 is also a powerful antiapoptotic agent influencing the apoptotic responses to a variety of agents of numerous cell types. These antiapoptotic actions tend to be mediated via the PI-3 kinase pathway, although this is again not exclusive, and there is considerable cross-talk between the two predominant signalling pathways.

The end results of these opposing effects of IGF-1 may be several-fold. First, there is increased proliferation and thus epithelial cell turnover within tissues. Second, the antiapoptotic effects cause an imbalance in the usual tight control between proliferation and cell death and result in hyperproliferation. This is the first stage in the development of many cancers and has been particularly well demonstrated in colorectal tumorigenesis in which it precedes the formation of colonic adenomas. Third, such an imbalance between cell proliferation and death would favour, even slightly, survival of stem cells that had undergone early genetic 'hits'.^[4] This would increase the pool of damaged cells available for second and subsequent hits. Higher levels of IGF-1 would be expected to activate survival pathways that would make programmed cell death of damaged cells slightly less probable. When applied overall to a large number of 'at risk' cells over many years, even a small influence in favour of survival of such cells could accelerate carcinogenesis, although not initiate cancer development per se.

SOURCES OF APIGENIN

Apigenin is an antioxidant flavonoid found in herbs, spices and other food plants. Examples of foods that contain apigenin are the herbs and spices, coriander, licorice, marjoram, parsley, oregano, rosemary and tarragon. Other foods such a citrus, tea, celery and wheat also contain significant quantities of this yellow cancer fighting compound.

apigenin inhibits IGF1

Apigenin suppresses insulin-like growth factor I receptor signaling in human prostate cancer: an in vitro and in vivo study.

Shukla S, Gupta S.

Department of Urology, Case Western Reserve University, Cleveland, Ohio 44106, USA.

Abstract

Deregulation of insulin-like growth factor (IGF)-I/IGF-IR signaling has been implicated in the development and progression of prostate cancer. Agents that can suppress the mitogenic activity of the IGF/IGF-IR growth axis may be of preventive or therapeutic value. We have previously demonstrated that apigenin, a plant flavone, modulates IGF signaling through upregulation of IGFBP-3. In this study, we investigated the mechanism(s) of apigenin action on the IGF/IGF-IR signaling pathway. Exposure of human prostate cancer DU145 cells to apigenin markedly reduced IGF-I-stimulated cell proliferation and induced apoptosis. Apigenin inhibited IGF-I-induced activation of IGF-IR and Akt in DU145 cells. Similar growth inhibitory and apoptotic responses were observed in PC-3 cells, which constitutively overexpress this pathway. This effect of apigenin appears to be due partially to reduced autophosphorylation of IGF-IR. Inhibition of p-Akt by apigenin resulted in decreased phosphorylation of GSK-3beta along with decreased expression of cyclin D1 and increased expression of p27/kip1. In vivo administration of apigenin to PC-3 tumor xenografts inhibited tumor growth, resulted in IGF-IR inactivation and dephosphorylation of Akt and its downstream signaling. These results suggest that inhibition of cell proliferation and induction of apoptosis by apigenin are mediated, at least in part, by its ability to inhibit IGF/IGF-IR signaling and the PI3K/Akt pathway.