Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95–2

Abstract

Obesity is one of the well-established risk factors for endometrial cancer. Recent clinical studies have demonstrated that circulating adiponectin concentrations are inversely correlated with the incidence of endometrial carcinoma. Such epidemiological findings are consistent with the paradoxical observations that adiponectin levels are reduced in obesity. This study investigated the direct effects of adiponectin on two endometrial carcinoma cell lines, HEC-1-A and RL95-2. These cell lines express both variants of adiponectin receptors, adipo-R1 and adipo-R2. Adiponectin treatment leads to suppression of cell proliferation in both cell types, which is primarily due to the significant increase of cell populations at G 1 /G 0 -phase and to the induction of apoptosis. The inhibition of growth in these two cell lines appears to be mediated by different signaling pathways. Although adiponectin treatment markedly increases the phosphorylation (Thr172) of AMP-activated protein kinase a in both HEC-1-A and RL95-2 within 30 min, prolonged exposure (48 h) leads to inactivation of Akt as well as reduction of cyclin D1 protein expression in HEC-1-A cells. In contrast, similar treatment of RL95-2 cells with adiponectin, while having no effects on Akt activity and cyclin D1 expression, causes a decrease in cyclin E2 expression and the activity of mitogen-activated kinase (p42/44). We conclude that adiponectin exerts direct anti-proliferative effects on HEC-1-A and RL95-2 cells by inducing cell cycle arrest and apoptosis. Depending on the genotypes of the endometrial cancer cells, the inhibitory effects of adiponectin are associated with the reduction of different pro-growth regulators of cell cycle and signaling proteins. Our study thus provides a cellular mechanism underlying the linkages between endometrial cancer and obesity.

Early gastric cancer shows different associations with adipose tissue volume depending on histological type

“…The mechanisms are not clear yet and require further investigation. However, recent studies have provided evidence that adipose tissue can produce many cytokines (adipokines), such as leptin and adiponectin, which can potently affect the biological behavior of malignant cells [41][42][43][44][45][46][47][48][49][50]. Our data support the hypothesis that these adipose tissue-derived factors are differently associated with the caricinogenesis or progression of GC of each histological type.…”

“…Recent studies have demonstrated that adipocytes produce a variety of secretory peptides, named adipokines [39,40]. More recently, some adipokines, such as leptin and adiponectin, have been shown to critically regulate the biological behavior of malignant cells [41][42][43][44][45][46][47][48][49][50], raising the possibility that adipocytes may have positive roles in the development of malignant diseases through the secretion of adipokines in an endocrine or intracrine manner. In addition, it has been suggested that the biochemical characteristics of visceral and subcutaneous adipose tissues are somewhat different [51,52].…”

Expression of Adiponectin Receptor 1 Is Indicative of Favorable Prognosis in Non-small Cell Lung Carcinoma

“…Therefore, there has been great interest in determining whether adiponectin has a protective role in carcinogenesis (Kelesidis et al 2006;Byeon et al 2010). Adiponectin has anti-angiogenic (Molica et al 2009), anti-proliferative (Dos Santos et al 2008;Benaitreau et al 2009), and proapoptotic effects, and also arrests cancer cell growth (Kang et al 2005;Cong et al 2007), having both direct effects on carcinogenesis and indirect effects through alteration of hor-mones and cytokine levels (Kelesidis et al 2006).…”

Obesity and Cancer: Concepts and Challenges

“…Serum levels of adiponectin have an inverse correlation with BMI and epidemiologic and preclinical data suggest a protective effect for increased adiponectin levels on obesity-related cancer risk [64][65][66][67].…”