Log in to search using one of your social media accounts:

 

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

Related Links:

Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Preclinical studies suggest statins may help prevent prostate cancer (PC), but epidemiologic results are mixed. Many epidemiological studies have relatively short prediagnosis drug exposure data, which may miss some statin use. We completed a nested case–control study investigating the impact of statin use on PC diagnosis and clinically significant PC using data from men aged ≥40 years in the Canadian province of Saskatchewan between 1990 and 2010. Drug exposure histories were derived from a population‐based prescription drug database. We used conditional logistic regression to model use of statins as a class an...
Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Cancer Therapy and Prevention Source Type: research
CONCLUSION: In this review article, we provide an overview of the current preclinical and clinical status of statins as antitumor agents. In addition, we evaluated various patents that describe the role of mevalonate pathway inhibitors and methods to determine if cancer cells are sensitive to statins treatment. PMID: 29189178 [PubMed - as supplied by publisher]
Source: Recent Patents on Anti-Cancer Drug Discovery - Category: Cancer & Oncology Tags: Recent Pat Anticancer Drug Discov Source Type: research
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
More News: Cancer | Cancer & Oncology | Cancer Therapy | Cholesterol | Drugs & Pharmacology | Study