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Total 55 results found since Jan 2013.

Metformin inhibits estrogen ‐dependent endometrial cancer cell growth by activating the AMPK–FOXO1 signal pathway
This study provide a novel mechanism of anti‐neoplastic effect for metformin through the regulation of FOXO1, and suggest that AMPK‐FOXO1 pathway may be a therapeutic target to the development of new anti‐neoplastic drugs.
Source: Cancer Science - November 24, 2016 Category: Cancer & Oncology Authors: Jingfang Zou, Liangli Hong, Chaohuan Luo, Zhi Li, Yuzhang Zhu, Tianliang Huang, Yongneng Zhang, Huier Yuan, Yaqiu Hu, Tengfei Wen, Wanling Zhuang, Bozhi Cai, Xin Zhang, Jiexiong Huang, Jidong Cheng Tags: Original Article Source Type: research

Hyperglycaemia-induced resistance to Docetaxel is negated by metformin: a role for IGFBP-2
The incidence of many common cancers varies between different populations and appears to be affected by a Western lifestyle. Highly proliferative malignant cells require sufficient levels of nutrients for their anabolic activity. Therefore, targeting genes and pathways involved in metabolic pathways could yield future therapeutics. A common pathway implicated in energetic and nutritional requirements of a cell is the LKB1/AMPK pathway. Metformin is a widely studied anti-diabetic drug, which improves glycaemia in patients with type 2 diabetes by targeting this pathway. We investigated the effect of metformin on prostate can...
Source: Endocrine-Related Cancer - November 20, 2016 Category: Endocrinology Authors: Biernacka, K. M., Persad, R. A., Bahl, A., Gillatt, D., Holly, J. M. P., Perks, C. M. Tags: Research Source Type: research

Metformin potentiates anti-tumor effect of resveratrol on pancreatic cancer by down-regulation of VEGF-B signaling pathway.
Authors: Zhu M, Zhang Q, Wang X, Kang L, Yang Y, Liu Y, Yang L, Li J, Yang L, Liu J, Li Y, Zu L, Shen Y, Qi Z Abstract Our previous study showed that resveratrol (RSV) exhibited not only anti-tumor effect, but also had potential tumor promotion effect on pancreatic cancer (Paca) cells through up-regulation of VEGF-B. We determined whether metformin (MET) could potentiate the anti-tumor effect of RSV on PaCa in this study. Combination of RSV (100 μmol/l) and MET (20 mmol/l) significantly inhibited tumor growth and increased apoptosis of human PaCa in comparison with RSV or MET alone treatment in PaCa cell lines (Mi...
Source: Oncotarget - October 6, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

TRAIL restores DCA/metformin-mediated cell death in hypoxia.
Abstract Previous studies have shown that hypoxia can reverse DCA/metformin-induced cell death in breast cancer cells. Therefore, targeting hypoxia is necessary for therapies targeting cancer metabolism. In the present study, we found that TRAIL can overcome the effect of hypoxia on the cell death induced by treatment of DCA and metformin in breast cancer cells. Unexpectedly, DR5 is upregulated in the cells treated with DCA/metformin, and sustained under hypoxia. Blocking DR5 by siRNA inhibited DCA/metformin/TRAIL-induced cell death, indicating that DR5 upregulation plays an important role in sensitizing cancer ce...
Source: Biochemical and Biophysical Research communications - August 24, 2016 Category: Biochemistry Authors: Hong SE, Kim CS, An S, Kim HA, Hwang SG, Song JY, Lee JK, Hong J, Kim JI, Noh WC, Jin HO, Park IC Tags: Biochem Biophys Res Commun Source Type: research

Metformin elicits antitumor effects and downregulates the histone methyltransferase multiple myeloma SET domain (MMSET) in prostate cancer cells
CONCLUSIONSThese data suggest MMSET may play a role in the inhibitory effect of metformin on PCa and could serve as a potential novel therapeutic target for PCa. Prostate © 2016 Wiley Periodicals, Inc.
Source: The Prostate - July 11, 2016 Category: Urology & Nephrology Authors: Nicole M. A. White‐Al Habeeb, Julia Garcia, Neil Fleshner, Bharati Bapat Tags: Original Article Source Type: research

The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in malignancy of human endometrial cancer cells.
Authors: Shimada H, Satohisa S, Kohno T, Takahashi S, Hatakeyama T, Konno T, Tsujiwaki M, Saito T, Kojima T Abstract Lipolysis-stimulated lipoprotein receptor (LSR) has been identified as a novel molecular constituent of tricellular contacts that have a barrier function for the cellular sheet. LSR recruits tricellulin (TRIC), which is the first molecular component of tricellular tight junctions. Knockdown of LSR increases cell motility and invasion of certain cancer cells. However, the behavior and the roles of LSR in endometrial cancer remain unknown. In the present study, we investigated the behavior and roles of...
Source: Oncotarget - April 3, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Activation of autophagy flux by metformin downregulates cellular FLICE-like inhibitory protein and enhances TRAIL- induced apoptosis.
In this study, we demonstrated that metformin could induce TRAIL-mediated apoptotic cell death in TRAIL-resistant human lung adenocarcinoma A549 cells. Pretreatment of metformindownregulation of c-FLIP and markedly enhanced TRAIL-induced tumor cell death by dose-dependent manner. Treatment with metformin resulted in slight increase in the accumulation of microtubule-associated protein light chain LC3-II and significantly decreased the p62 protein levels by dose-dependent manner indicated that metformin induced autophagy flux activation in the lung cancer cells. Inhibition of autophagy flux using a specific inhibitor and ge...
Source: Oncotarget - March 19, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells
Abstract Metformin, which is a drug commonly prescribed to treat type 2 diabetes, has anti-proliferative effects in cancer cells; however, the molecular mechanisms underlying this effect remain largely unknown. The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells. p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantitative RT-PCR, Western blots, and promoter activity assay. Breast cancer cells were transfected with siRNA against T...
Source: Breast Cancer Research and Treatment - March 8, 2016 Category: Cancer & Oncology Source Type: research

Metformin inhibits growth of human non-small cell lung cancer cells via liver kinase B-1-independent activation of adenosine monophosphate-activated protein kinase.
Authors: Guo Q, Liu Z, Jiang L, Liu M, Ma J, Yang C, Han L, Nan K, Liang X Abstract Metformin, the most widely administered oral anti‑diabetic therapeutic agent, exerts its glucose-lowering effect predominantly via liver kinase B1 (LKB1)-dependent activation of adenosine monophosphate-activated protein kinase (AMPK). Accumulating evidence has demonstrated that metformin possesses potential antitumor effects. However, whether the antitumor effect of metformin is via the LKB1/AMPK signaling pathway remains to be determined. In the current study, the effects of metformin on proliferation, cell cycle progression, and...
Source: Molecular Medicine Reports - February 9, 2016 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Anti-cancer effect of metformin by suppressing signaling pathway of HER2 and HER3 in tamoxifen-resistant breast cancer cells
Abstract Development of new therapeutic strategies is becoming increasingly important to overcome tamoxifen resistance. Recently, much interest has been focused on anti-tumor effects of metformin commonly used to treat type II diabetes. Increased protein expression and signaling of epidermal growth factor receptor (EGFR) family is a possible mechanism involved in tamoxifen resistance. Since HER2/HER3 heterodimers are able to induce strong downstream signaling and activate various biological responses such as cellular proliferation and growth, we investigated the anti-cancer effect of metformin by inhibition of sig...
Source: Tumor Biology - November 18, 2015 Category: Cancer & Oncology Source Type: research

Abstract 4969: Metformin causes AR degradation via Skp2-mediated ubiquitination
This study supports that use of metformin in combination with Enza or other ARSI drugs may not only block autophagy survival but also cause AR degradation that leads to PC cell death.Citation Format: Joy C. Yang, Allen C. Gao, Christopher P. Evans. Metformin causes AR degradation via Skp2-mediated ubiquitination. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4969. doi:10.1158/1538-7445.AM2015-4969
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Yang, J. C., Gao, A. C., Evans, C. P. Tags: Molecular and Cellular Biology Source Type: research

Abstract 3814: Metformin induces ER stress-dependent apoptosis through miR-708-5p/NNAT pathway in prostate cancer
In this study, we identified miR-708-5p as a novel downstream effector of metformin in prostate cancer. By increasing the expression of miR-708-5p, metformin suppresses the expression of endoplasmic reticulum (ER) membrane protein neuronatin (NNAT) and subsequently induces apoptosis of prostate cancer cells through ER stress pathway. Notably, down-regulated NNAT is associated with down-regulated intracellular calcium level and induces malformation of endoplasmic reticulum-ribosome structure which is revealed by electronic microscopy. Furthermore, western blot shows that the unfolded-protein response (UPR) proteins includin...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Yang, J., Wei, J., Wu, Y., Wang, Z., Guo, Y., Li, X. Tags: Molecular and Cellular Biology Source Type: research

Abstract 16: Combination simvastatin and metformin induces G1-phase cell cycle arrest and Ripk1- and Ripk3-dependent necroptosis in C4-2B osseous metastatic castration-resistant prostate cancer cells
Castration-resistant prostate cancer (CRPC) cells acquire resistance to chemotherapy and apoptosis in part due to enhanced aerobic glycolysis and biomass production, known as Warburg effect. We previously demonstrated that combination simvastatin (SIM) and metformin (MET) ameliorates critical Warburg effect-related metabolic aberrations of C4-2B cells, synergistically and significantly decreases CRPC cell viability and metastatic properties, with minimal effect on normal prostate epithelial cells, and inhibits primary prostate tumor growth, metastasis, and biochemical failure in an orthotopic model of metastatic CRPC, more...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Babcook, M. A., Sramkoski, R. M., Fujioka, H., Daneshgari, F., Almasan, A., Shukla, S., Gupta, S. Tags: Molecular and Cellular Biology Source Type: research

Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog signaling pathway in breast cancer.
Abstract Metformin, a widely prescribed antidiabetic drug, has previously been shown to lower the risk of certain types of cancer, including that of breast cancer, and to improve prognosis. Its anticancer effects, which are mediated by the activation of AMP-activated protein kinase (AMPK), have become notable. The Sonic hedgehog (Shh) signaling pathway is involved in changes in mammary ducts and malignant transformation. The aim of the present study was to elucidate the role of the Shh pathway in mediating the anticancer effects of metformin and the correlation between AMPK and the Shh pathway. We investigated t...
Source: International Journal of Molecular Medicine - May 21, 2015 Category: Molecular Biology Authors: Fan C, Wang Y, Liu Z, Sun Y, Wang X, Wei G, Wei J Tags: Int J Mol Med Source Type: research

Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the downregulation of insulin-like growth factor 1 receptor.
Abstract Metformin is a biguanide drug that is widely used for the treatment of type 2 diabetes. Recent studies have shown that metformin inhibits cancer cell proliferation and tumor growth both in vitro and in vivo. The anti-tumor mechanisms of metformin include activation of the AMP-activated protein kinase/mTOR pathway and direct inhibition of insulin/insulin-like growth factor (IGF)-mediated cellular proliferation. However, the anti-tumor mechanism in prostate cancer remains unclear. Because activation of the IGF-1 receptor (IGF-1R) is required for prostate cell proliferation, IGF-1R inhibitors may be of the...
Source: Biochemical and Biophysical Research communications - April 7, 2015 Category: Biochemistry Authors: Kato H, Sekine Y, Furuya Y, Miyazawa Y, Koike H, Suzuki K Tags: Biochem Biophys Res Commun Source Type: research