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Rich66 · 01-22-2010, 12:10 AM

Oncogene. 2008 Jun 5;27(25):3576-86. Epub 2008 Jan 21.
The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level.

Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, Tanti JF, Le Marchand-Brustel Y, Bost F.
INSERM U568, Nice, France.
Metformin is a widely used antidiabetic agent, which regulates glucose homeostasis through inhibition of liver glucose production and an increase in muscle glucose uptake. Recent studies suggest that metformin may reduce the risk of cancer, but its mode of action in cancer remains not elucidated. We investigated the effect of metformin on human prostate cancer cell proliferation in vitro and in vivo. Metformin inhibited the proliferation of DU145, PC-3 and LNCaP cancer cells with a 50% decrease of cell viability and had a modest effect on normal prostate epithelial cell line P69. Metformin did not induce apoptosis but blocked cell cycle in G(0)/G(1). This blockade was accompanied by a strong decrease of cyclin D1 protein level, pRb phosphorylation and an increase in p27(kip) protein expression. Metformin activated the AMP kinase pathway, a fuel sensor signaling pathway. However, inhibition of the AMPK pathway using siRNA against the two catalytic subunits of AMPK did not prevent the antiproliferative effect of metformin in prostate cancer cells. Importantly, oral and intraperitoneal treatment with metformin led to a 50 and 35% reduction of tumor growth, respectively, in mice bearing xenografts of LNCaP. Similar, to the in vitro study, metformin led to a strong reduction of cyclin D1 protein level in tumors providing evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent epidemiological studies.

Front Biosci. 2008 May 1;13:3273-87.
The type I insulin-like growth factor receptor pathway: a key player in cancer therapeutic resistance.

Casa AJ, Dearth RK, Litzenburger BC, Lee AV, Cui X.
Breast Center, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract

The insulin-like growth factor (IGF) ligands stimulate cellular proliferation and survival by activating the type I insulin-like growth factor receptor (IGF-IR). As a result, the IGF signaling system is implicated in a number of cancers, including those of the breast, prostate, and lung. In addition to mitogenic and anti-apoptotic roles that may directly influence tumor development, IGF-IR also appears to be a critical determinant of response to numerous cancer therapies. This review describes the role of the IGF-IR pathway in mediating resistance to both general cytotoxic therapies, such as radiation and chemotherapy, and targeted therapies, such as tamoxifen and trastuzumab. It concludes with a description of approaches to target IGF-IR and argues that inhibition of IGF signaling, in conjunction with standard therapies, may enhance the response of cancer cells to multiple modalities.

PMID: 18508432 [PubMed - indexed for MEDLINE]

ACTOPLUS MET combines two antihyperglycemic agents with different mechanisms of action to improve glycemic control in patients with type 2 diabetes: pioglitazone hydrochloride, a member of the thiazolidinedione class, and metformin hydrochloride, a member of the biguanide class. Thiazolidinediones are insulin-sensitizing agents that act primarily by enhancing peripheral glucose utilization, whereas biguanides act primarily by decreasing endogenous hepatic glucose production.

http://www.themoneytimes.com/feature...-10115966.html

A new study suggests that a low-dose combination therapy using [COLOR=#009600 ! important][COLOR=#009600 ! important]GlaxoSmithKline[/COLOR][/COLOR]

(GSK) Avandia and anti-[COLOR=#009600 ! important][COLOR=#009600 ! important]diabetic [COLOR=#009600 ! important]treatment[/COLOR][/COLOR][/COLOR]

metformin may help prevent progression to type 2 diabetes by two-thirds in people at risk of the ailment. According to experts, Avandia, also known as [COLOR=#009600 ! important][COLOR=#009600 ! important]rosiglitazone[/COLOR][/COLOR]

and metformin both lower the development of diabetes in patients with impaired glucose tolerance (IGT).

However, both the drugs work differently. While, Avandia is known to increase insulin sensitivity, metformin reduces liver glucose production.

01-22-2010, 12:10 AM	#28
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: Common Diabetes Drug May 'Revolutionize' Cancer Therapies: Unexpected T-cell Brea Oncogene. 2008 Jun 5;27(25):3576-86. Epub 2008 Jan 21. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, Tanti JF, Le Marchand-Brustel Y, Bost F. INSERM U568, Nice, France. Metformin is a widely used antidiabetic agent, which regulates glucose homeostasis through inhibition of liver glucose production and an increase in muscle glucose uptake. Recent studies suggest that metformin may reduce the risk of cancer, but its mode of action in cancer remains not elucidated. We investigated the effect of metformin on human prostate cancer cell proliferation in vitro and in vivo. Metformin inhibited the proliferation of DU145, PC-3 and LNCaP cancer cells with a 50% decrease of cell viability and had a modest effect on normal prostate epithelial cell line P69. Metformin did not induce apoptosis but blocked cell cycle in G(0)/G(1). This blockade was accompanied by a strong decrease of cyclin D1 protein level, pRb phosphorylation and an increase in p27(kip) protein expression. Metformin activated the AMP kinase pathway, a fuel sensor signaling pathway. However, inhibition of the AMPK pathway using siRNA against the two catalytic subunits of AMPK did not prevent the antiproliferative effect of metformin in prostate cancer cells. Importantly, oral and intraperitoneal treatment with metformin led to a 50 and 35% reduction of tumor growth, respectively, in mice bearing xenografts of LNCaP. Similar, to the in vitro study, metformin led to a strong reduction of cyclin D1 protein level in tumors providing evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent epidemiological studies. Front Biosci. 2008 May 1;13:3273-87. The type I insulin-like growth factor receptor pathway: a key player in cancer therapeutic resistance. Casa AJ, Dearth RK, Litzenburger BC, Lee AV, Cui X. Breast Center, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Abstract The insulin-like growth factor (IGF) ligands stimulate cellular proliferation and survival by activating the type I insulin-like growth factor receptor (IGF-IR). As a result, the IGF signaling system is implicated in a number of cancers, including those of the breast, prostate, and lung. In addition to mitogenic and anti-apoptotic roles that may directly influence tumor development, IGF-IR also appears to be a critical determinant of response to numerous cancer therapies. This review describes the role of the IGF-IR pathway in mediating resistance to both general cytotoxic therapies, such as radiation and chemotherapy, and targeted therapies, such as tamoxifen and trastuzumab. It concludes with a description of approaches to target IGF-IR and argues that inhibition of IGF signaling, in conjunction with standard therapies, may enhance the response of cancer cells to multiple modalities. PMID: 18508432 [PubMed - indexed for MEDLINE] ACTOPLUS MET combines two antihyperglycemic agents with different mechanisms of action to improve glycemic control in patients with type 2 diabetes: pioglitazone hydrochloride, a member of the thiazolidinedione class, and metformin hydrochloride, a member of the biguanide class. Thiazolidinediones are insulin-sensitizing agents that act primarily by enhancing peripheral glucose utilization, whereas biguanides act primarily by decreasing endogenous hepatic glucose production. http://www.themoneytimes.com/feature...-10115966.html A new study suggests that a low-dose combination therapy using [COLOR=#009600 ! important][COLOR=#009600 ! important]GlaxoSmithKline[/COLOR][/COLOR] (GSK) Avandia and anti-[COLOR=#009600 ! important][COLOR=#009600 ! important]diabetic [COLOR=#009600 ! important]treatment[/COLOR][/COLOR][/COLOR] metformin may help prevent progression to type 2 diabetes by two-thirds in people at risk of the ailment. According to experts, Avandia, also known as [COLOR=#009600 ! important][COLOR=#009600 ! important]rosiglitazone[/COLOR][/COLOR] and metformin both lower the development of diabetes in patients with impaired glucose tolerance (IGT). However, both the drugs work differently. While, Avandia is known to increase insulin sensitivity, metformin reduces liver glucose production. __________________ Mom's treatment history (link)