Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells (original) (raw)
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Effects of adiponectin on breast cancer cell growth and signaling
British journal of cancer, 2008
Obesity is a risk factor for postmenopausal breast cancer. Adiponectin/Acrp30 is lower in obese individuals and may be negatively regulating breast cancer growth. Here we determined that five breast cancer cell lines, MDA-MB-231, MDA-MB-361, MCF-7, T47D, and SK-BR-3, expressed one or both of the Acrp30 receptors. In addition, we found that the addition of Acrp30 to MCF-7, T47D, and SK-BR-3 cell lines inhibited growth. Oestrogen receptor (ER) positive MCF-7 and T47D cells were inhibited at lower Acrp30 concentrations than ER-negative SK-BR-3 cells. Growth inhibition may be related to apoptosis since PARP cleavage was increased by Acrp30 in the ER-positive cell lines. To investigate the role of ER in the response of breast cancer cells to Acrp30, we established the MDA-ERalpha7 cell line by insertion of ER-alpha into ER-alpha-negative MDA-MB-231 cells. This line readily formed tumours in athymic mice and was responsive to oestradiol in vivo. In vitro, MDA-ERalpha7 cells were growth in...
British journal of cancer, 2008
Serum levels of adiponectin are inversely associated with breast cancer risk. In this study, its effect on growth and gene expression of MCF-7 breast cancer cells and MCF-10A human mammary epithelial cells was compared. The antiproliferative effect of adiponectin on MCF-10A cells was more pronounced and was accompanied by elevated transcript levels of caspase 1, ERbeta2, ERbeta5, TR2 and USP2. Our data suggest that upregulation of genes with known growth inhibitory or apoptotic functions in mammary epithelial cells might contribute to the protective action of this adipocytokine.
Endocrine-Related Cancer, 2007
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 G1/G0-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 α in both...
Adiponectin effects on human breast cancer cells are dependent on 17-β estradiol
Oncology Reports, 2008
Adiponectin, an adipocyte-derived serum protein, is known to positively affect the glucose and lipid metabolism and these effects are mediated by its receptors, AdipoR1 and R2. Serum adiponectin levels are inversely associated with breast cancer risk, but the molecular mechanisms underlying this association are not fully elucidated. Thus, the purpose of this study was to investigate the influence of adiponectin on breast cancer cells in vitro. We were able to demonstrate the expression of AdipoR1 and R2 in MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cells on the mRNA level. Furthermore, the AdipoR1 protein could be detected by immunoblot analysis. In MCF-7 breast cancer cells, the expression of AdipoR1 significantly declined after stimulation with 17-ß estradiol, whereas the cyclin A2 expression significantly increased. Both effects were inhibited by the addition of adiponectin. Treatment with different concentrations of adiponectin in steroid-hormone-free medium did not affect cell proliferation or apoptosis. In contrast, after the addition of 17-ß estradiol, adiponectin slightly decreased the growth of the MDA-MB-231 and SK-BR3 cells but increased proliferation of the hormone-dependent MCF-7 breast cancer cells. Adiponectin also triggered cellular apoptosis in MDA-MB-231 breast cancer cells in the presence of 17-ß estradiol. These findings suggest that a cross-talk between adiponectin and estrogen receptor signaling exists in breast cancer cells and that adiponectin effects on the growth and apoptosis of breast cancer cells in vitro are dependent on the presence of 17-ß estradiol.
The Role of Adiponectin in Cancer: A Review of Current Evidence
Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents.
Adiponectin as Link Factor between Adipose Tissue and Cancer
International Journal of Molecular Sciences
Adipose tissue is a key regulator of energy balance playing an active role in lipid storage as well as in synthesizing several hormones directly involved in the pathogenesis of obesity. Obesity represents a peculiar risk factor for a growing list of cancers and is frequently associated to poor clinical outcome. The mechanism linking obesity and cancer is not completely understood, but, amongst the major players, there are both chronic low-grade inflammation and deregulation of adipokines secretion. In obesity, the adipose tissue is pervaded by an abnormal number of immune cells that create an inflammatory environment supporting tumor cell proliferation and invasion. Adiponectin (APN), the most abundant adipokine, shows anti-inflammatory, anti-proliferative and pro-apoptotic properties. Circulating levels of APN are drastically decreased in obesity, suggesting that APN may represent the link factor between obesity and cancer risk. The present review describes the recent advances on t...
The Emerging Role of Adiponectin in Female Malignancies
International Journal of Molecular Sciences
Obesity, characterized by excess body weight, is now accepted as a hazardous health condition and an oncogenic factor. In different epidemiological studies obesity has been described as a risk factor in several malignancies. Some biological mechanisms that orchestrate obesity–cancer interaction have been discovered, although others are still not completely understood. The unbalanced secretion of biomolecules, called “adipokines”, released by adipocytes strongly influences obesity-related cancer development. Among these adipokines, adiponectin exerts a critical role. Physiologically adiponectin governs glucose levels and lipid metabolism and is fundamental in the reproductive system. Low adiponectin circulating levels have been found in obese patients, in which its protective effects were lost. In this review, we summarize the epidemiological, in vivo and in vitro data in order to highlight how adiponectin may affect obesity-associated female cancers.
The Open Obesity Journal, 2010
Adiponectin is an adipose tissue-derived hormone. It is a key hormone that is responsible for insulin sensitization, and its circulating level is inversely associated with abdominal obesity. Recent studies have shown that a reduced plasma adiponectin level is significantly correlated with the risk of various kinds of cancers. Adiponectin may influence the cancer risk by modulating the metabolic environment indirectly. However several cancer cells express adiponectin receptors, suggesting that adiponectin also may modulate the cancer progression directly. Herein, we review the recent evidence concerning the molecular mechanisms linking adiponectin receptor signaling and cancer. Further studies are required to fully elucidate the molecular mechanisms of the adiponectin-mediated signaling pathway in cancer.
Multifaceted roles of Adiponectin in cancer
Best Practice & Research Clinical Endocrinology & Metabolism, 2014
Obesity is linked to increased cancer risk. Pathological expansion of adipose tissue impacts adipocyte function and secretion of hormonal factors regulating tissue homeostasis and metabolism. Adiponectin is an adipocytesecreted, circulating hormone with pleiotropic functions in lipid and glucose metabolism, and beneficial roles in cardiovascular functions and inflammation. In obesity, decreased Adiponectin plasma levels correlate with tumor development and progression. The association of Adiponectin with potential tumor-limiting functions has raised significant interest in exploring this adipokine as a target for cancer-diagnostic and therapeutic applications. Recent studies, however, also implicate Adiponectin in supporting malignancy. This review highlights the evidence that links Adiponectin signaling to either cancer-protective or cancer-supporting functions. In this context, we discuss Adiponectin interactions with its receptors and associated signaling pathways. Despite significant advances in understanding Adiponectin functions and signaling mechanisms, its role in cancer remains multifaceted and subject to controversy.