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Targeting energy metabolism of cancer cells: Combined administration of NCL-240 and 2-DG

Publication date: 30 October 2017 Source:International Journal of Pharmaceutics, Volume 532, Issue 1 Author(s): Bhushan S. Pattni, Aditi Jhaveri, Ivy Dutta, James D. Baleja, Alexei Degterev, Vladimir Torchilin Cancer cells increase their metabolism to produce the energy and biomolecules necessary for growth and proliferation. Thus, energy metabolism pathways may serve as targets for anti-cancer therapy. NCL-240 is a second generation anti-cancer drug belonging to the PITenins class of PI3K-Akt inhibitors. Our analysis suggested that NCL-240 caused disruptions in mitochondrial oxidative phosphorylation and up-regulated glycolysis, as evidenced by the loss of NMR peaks for the amino acid products derived from the TCA cycle along with presence of only lactate peaks and the loss of glucose peaks. NCL-240 was combined with 2-deoxy-d-glucose (2-DG) in early proof-of-concept studies on multiple cell lines. 2-DG enhanced cell death response to NCL-240 administration, with cytotoxicity results similar to those under hypoglycemic conditions. In further studies, NCL-240 encapsulated in phosphatidylcholine/cholesterol liposomes was combined with freely dissolved 2-DG. Cell cycle analysis of sensitive and resistant strains of A2780 cells treated with combinations of NCL-240/2-DG pointed to a G0/G1 phase arrest for 80–90% of the total, indicating an inability to grow and divide. Cytotoxicity studies with in vitro cancer cell monolayer models confirmed the results of cell cycle analy...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research

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Publication date: 1 January 2018 Source:Colloids and Surfaces B: Biointerfaces, Volume 161 Author(s): Sudipta Mallick, Le Thi Thuy, Seulgi Lee, Jong-II Park, Joon Sig Choi • Mitochondria are exclusively employed to produce energy required for the vital metabolic functions of the cell. However, mitochondria also play a key role in mammalian cell death. Dissipation in the mitochondria membrane potential causes cell death. Therefore, in cancer therapy, mitochondria are a novel target. Herein, we developed a nano-formulation of Antimycin A specifically targeted towards mitochondria and lung cancer; A549 cell. The liposom...
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research
Simvastatin inhibits the expression of stemness‑related genes and the metastatic invasion of human cancer cells via destruction of the cytoskeleton. Int J Oncol. 2017 Oct 13;: Authors: Tatè R, Zona E, De Cicco R, Trotta V, Urciuoli M, Morelli A, Baiano S, Carnuccio R, Fuggetta MP, Morelli F Abstract Statins are a class of drugs that inhibit the rate-limiting steps in the cholesterol biosynthesis pathway. They act by inhibiting 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate. Blocking of mevalonate synthesis leads to inhibition of the...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
We presented a promising method for relieving the hypoxia degree in solid tumors and down-regulating HIF-1α protein by directly delivering oxygen into tumors, which will be very helpful for subsequent cancer therapy. Graphical abstract
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research
Abstract Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physico-chemical and biological properties, making them attractive for application in theranostics. However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th)1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells. While unable to affect T cells directly, GQD impaired the differentiation and function...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research
Lung adenocarcinoma accounts for ~40% of lung cancers, the leading cause of cancer-related death worldwide, and current therapies provide only limited survival benefit. Approximately half of lung adenocarcinomas harbor mutations in TP53 (p53), making these mutants appealing targets for lung cancer therapy. As mutant p53 remains untargetable, mutant p53-dependent phenotypes represent alternative targeting opportunities, but the prevalence and therapeutic relevance of such effects (gain of function and dominant-negative activity) in lung adenocarcinoma are unclear. Through transcriptional and functional analysis of murine Kr...
Source: Genes and Development - Category: Genetics & Stem Cells Authors: Tags: Research Papers Source Type: research
Publication date: Available online 25 July 2017 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Hongwang Wang, Asanka S. Yapa, Nilusha L. Kariyawasam, Tej B. Shrestha, Sebastian O. Wendel, Jing Yu, Marla Pyle, Matthew T. Basel, Aruni P. Malalasekera, Yubisela Toledo, Raquel Ortega, Prem S. Thapa, Hongzhou Huang, Susan X. Sun, Paul E. Smith, Deryl L. Troyer, Stefan H. Bossmann A novel type of supramolecular aggregate, named a “nanosponge” was synthesized through the interaction of novel supramolecular building blocks with trigonal geometry. The cholesterol-(K/D)nDEVDGC)3-trimaleimide unit c...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research
Publication date: Available online 12 July 2017 Source:Journal of Bioscience and Bioengineering Author(s): Satomi Yabuuchi, Satoshi Endo, KeangOk Baek, Kunihide Hoshino, Yoshio Tsujino, Mun'delanji C. Vestergaard, Masahiro Takagi Certain food ingredients can stimulate the human immune system. A lectin, concanavalin A (ConA), from Canavalia ensiformis (jack bean) is one of the most well-known food-derived immunostimulants and mediates activation of cell-mediated immunity through T cell proliferation. Generally, T cell activation is known to be triggered by the interaction between T cells and antigen-presenting cells (APCs)...
Source: Journal of Bioscience and Bioengineering - Category: Biomedical Science Source Type: research
Authors: Yazdi Rouholamini SE, Moghassemi S, Maharat Z, Hakamivala A, Kashanian S, Omidfar K Abstract Silibinin is a natural flavonoid with a strong antioxidant property and weak cytotoxic activity. It has demonstrated anti-tumoural activity against many types of malignancies; however, due to its hydrophobic structure, it has poor water solubility, bioavailability and permeability across intestinal epithelial cells. To improve the effect of silibinin, we have vehiculated silibinin by a highly stable niosomal nanostructure based on a Span 60/cholesterol (CH)/N-trimethyl chitosan (TMC) system in order to study its po...
Source: Artificial Cells, Nanomedicine and Biotechnology - Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research
Authors: Caldwell S Abstract Non-alcoholic steatohepatitis (NASH) is the more aggressive form of non-alcoholic fatty liver disease (NAFLD). NASH can progress to hepatic fibrosis, cirrhosis, portal hypertension and primary liver cancer. Therapy is evolving with a substantial number of trials of promising new agents now in progress. In this article however, we will examine data for several older forms of therapy which have been fairly extensively studied over the years: Polyunsaturated Fatty Acid (PUFA) supplements, vitamin E, insulin sensitizing agents with a focus on pioglitazone and statin agents. Early interest i...
Source: Clinical and molecular hepatology - Category: Gastroenterology Tags: Clin Mol Hepatol Source Type: research
This study identified 1,497 genes with significantly different expression at different ages. Gene sets with a defined age-associated expression pattern provide information about molecular processes with altered activity during aging and provide a valuable diagnostic tool for determining individual biological rate of aging and predicting risk of age-associated disease, as demonstrated in follow-up analyses. On a gene-by-gene basis, differential expression alone is insufficient to distinguish between genes that play a causative role in aging and genes that merely respond to the altered physiological environment in an aging o...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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