Search results for "AMPK"
showing 10 items of 53 documents
Glycolytic phenotype and AMP kinase modify the pathologic response of tumor xenografts to VEGF neutralization.
2011
Abstract VEGF antagonists are now widely used cancer therapeutics, but predictive biomarkers of response or toxicity remain unavailable. In this study, we analyzed the effects of anti-VEGF therapy on tumor metabolism and therapeutic response by using an integrated set of imaging techniques, including bioluminescence metabolic imaging, 18-fluorodeoxyglucose positron emission tomography, and MRI imaging and spectroscopy. Our results revealed that anti-VEGF therapy caused a dramatic depletion of glucose and an exhaustion of ATP levels in tumors, although glucose uptake was maintained. These metabolic changes selectively accompanied the presence of large necrotic areas and partial tumor regress…
Advances in Targeting Signal Transduction Pathways
2012
// James A. McCubrey 1 , Linda S. Steelman 1 , William H. Chappell 1 , Lin Sun 1,2 , Nicole M. Davis 1 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Lucio Cocco 3 , Camilla Evangelisti 4 , Francesca Chiarini 4 , Alberto M. Martelli 3,4 , Massimo Libra 5 , Saverio Candido 5 , Giovanni Ligresti 5 , Grazia Malaponte 5 , Maria C. Mazzarino 5 , Paolo Fagone 5 , Marco Donia 5 , Ferdinando Nicoletti 5 , Jerry Polesel 6 , Renato Talamini 6 , Jorg Basecke 7 , Sanja Mijatovic 8 , Danijela Maksimovic-Ivanic 8 , Michele Milella 9 , Agostino Tafuri 10 , Joanna Dulinska-Litewka 11 , Piotr Laidler 11 , Antonio B. D’Assoro 12 , Lyudmyla Drobot 13 , Kazuo Umezawa 14 , Giuseppe Montalto 15 , Melchiorre Cer…
Cardioprotective effects of phytopigments via multiple signaling pathways.
2021
Abstract Background Cardiovascular diseases (CVDs) are among the deadliest non-communicable diseases, and millions of dollars are spent every year to combat CVDs. Unfortunately, the multifactorial etiology of CVDs complicates the development of efficient therapeutics. Interestingly, phytopigments show significant pleiotropic cardioprotective effects both in vitro and in vivo. Purpose This review gives an overview of the cardioprotective effects of phytopigments based on in vitro and in vivo studies as well as clinical trials. Methods A literature-based survey was performed to collect the available data on cardioprotective activities of phytopigments via electronic search engines such as Pub…
VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart
2014
Abstract Angiogenic growth factors have recently been linked to tissue metabolism. We have used genetic gain‐ and loss‐of function models to elucidate the effects and mechanisms of action of vascular endothelial growth factor‐B (VEGF‐B) in the heart. A cardiomyocyte‐specific VEGF‐B transgene induced an expanded coronary arterial tree and reprogramming of cardiomyocyte metabolism. This was associated with protection against myocardial infarction and preservation of mitochondrial complex I function upon ischemia‐reperfusion. VEGF‐B increased VEGF signals via VEGF receptor‐2 to activate Erk1/2, which resulted in vascular growth. Akt and mTORC1 pathways were upregulated and AMPK downregulated, …
Sub-lethal Doses of Polybrominated Diphenyl Ethers, in Vitro, Promote Oxidative Stress and Modulate Molecular Markers Related to Cell Cycle, Antioxid…
2019
In the present study, we evaluated the effects of different concentrations of the polybrominated diphenyl ethers (PBDEs) BDE-209, BDE-47 and BDE-99, on the vitality and oxidative stress of a HS-68 human cell culture exposed to the compounds for three days. The results showed that for this exposure time, only the highest concentrations produced a significant vitality reduction and oxidative stress induction (p <
Pinolenic acid ameliorates oleic acid-induced lipogenesis and oxidative stress via AMPK/SIRT1 signaling pathway in HepG2 cells
2019
Pinolenic acid (PLA), a natural compound isolated from pine nut oil, has been reported to exert bioactivity against lipid anabolism. Nonetheless, the underlying mechanisms still poorly elucidated. The aim of this study is to comprehensively demonstrate the effects of PLA on oleic acid (OA)-induced non-alcoholic fatty liver disease (NAFLD) and their relationship with the lipid metabolic regulation. The results demonstrated that treatment with PLA dramatically inhibited lipid accumulation, oxidative stress as well as inflammatory responses induced by oleic acid in HepG2 cells. PLA also obviously decreased the levels of cellular triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA),…
Effect of Methanolic Extract of Dandelion Roots on Cancer Cell Lines and AMP-Activated Protein Kinase Pathway
2017
Ethnomedicinal knowledge of plant-derived bioactives could help us in discovering new therapeutic compounds of great potential. Certainly, dandelion has been used in traditional ethno-medicinal systems (i.e., Chinese, Arabian, Indian, and Native American) to treat different types of cancer. Though, dandelion is highly vigorous, but the potential mode of action is still unclear. In the current study, the antiproliferative activity of methanolic extracts of dandelion root (MEDr) on cell viability of HepG2, MCF7, HCT116, and normal Hs27 was investigated. It was observed that MEDr (500 μg/mL) drastically decreased the growth of HepG2 cell line, while the effect on MCF7 and HCT116 cell lines was…
Leisure time physical activity is associated with improved HDL functionality in high cardiovascular risk individuals: a cohort study.
2020
Abstract Aims Physical activity has consistently been shown to improve cardiovascular health and high-density lipoprotein-cholesterol levels. However, only small and heterogeneous studies have investigated the effect of exercise on high-density lipoprotein functions. Our aim is to evaluate, in the largest observational study to date, the association between leisure time physical activity and a range of high-density lipoprotein functional traits. Methods The study sample consisted of 296 Spanish adults at high cardiovascular risk. Usual leisure time physical activity and eight measures of high-density lipoprotein functionality were averaged over two measurements, one year apart. Multivariabl…
Metformin Restores AMPK Alpha-Mediated Autophagy and Prevents Carfilzomib-Induced Cardiotoxicity In Vivo
2018
Abstract Introduction: Carfilzomib (Cfz) significantly prolongs progression-free survival in relapsed or refractory multiple myeloma patients, as highlighted in the ENDEAVOR trial. However, Cfz has high incidences of cardiotoxicity and heart failure, leading to treatment cessation. Thus, there is an imperative need for preventive therapies. The study aimed to i) establish an in vivo Cfz cardiotoxicity protocol, ii) investigate the molecular mechanism, identify molecular targets and iii) based on initial results, investigate the potential protective effect and mechanism of Metformin (Met). Methods: Male, C57BL/6 mice, were randomized in groups as following: Acute protocol (6 days): Control (…
Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy
2017
Fasting reduces glucose levels and protects mice against chemotoxicity, yet drugs that promote hyperglycemia are widely used in cancer treatment. Here, we show that dexamethasone (Dexa) and rapamycin (Rapa), commonly administered to cancer patients, elevate glucose and sensitize cardiomyocytes and mice to the cancer drug doxorubicin (DXR). Such toxicity can be reversed by reducing circulating glucose levels by fasting or insulin. Furthermore, glucose injections alone reversed the fasting-dependent protection against DXR in mice, indicating that elevated glucose mediates, at least in part, the sensitizing effects of rapamycin and dexamethasone. In yeast, glucose activates protein kinase A (P…