Publication date: Available online 2 February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Stephan C. Jahn, Mohamed Hassan M. Solayman, Ryan J. Lorenzo, Taimour Langaee, Peter W. Stacpoole, Margaret O. James
Dichloroacetate (DCA), commonly used to treat metabolic disorders, is under investigation as an anti-cancer therapy due to its ability to reverse the Warburg effect and induce apoptosis in tumor cells. While DCA's mechanism of action is well-studied, other factors that influence its potential as a cancer treatment have not been thoroughly investigated. Here we show that expression of glutathione transferase zeta 1 (GSTZ1), the enzyme responsible for conversion of DCA to its inactive metabolite, glyoxylate, is downregulated in liver cancer and upregulated in some breast cancers, leading to abnormal expression of the protein. The cellular concentration of chloride, an ion that influences the stability of GSTZ1 in the presence of DCA, was also found to be abnormal in tumors, with consistently higher concentrations in hepatocellular carcinoma than in surrounding non-tumor tissue. Finally, results from experiments employing two- and three-dimensional cultures of HepG2 cells, parental and transduced to express GSTZ1, demonstrate that high levels of GSTZ1 expression confers resistance to the effect of high concentrations of DCA on cell viability. These results may have important clinical implications in determining intratumoral metabolism of DCA and, consequently, appropriate oral dosing.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1nG8A6P
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Background Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extrac...
-
UM-Chor1: establishment and characterization of the first validated clival chordoma cell line. J Neurosurg. 2017 Apr 21;:1-9 Authors:...
-
Publication date: Available online 10 May 2017 Source: Journal of Dairy Science Author(s): R.E. Vibart, M. Tavendale, D. Otter, B.H. Schw...
-
Competency-based psychiatric education for Indian medical undergraduates Vijayalakshmi Pernenkil Archives of Mental Health 2019 20(1):1-2 Be...
-
Related Articles Developmental control of macrophage function. Curr Opin Immunol. 2017 Dec 13;50:64-74 Authors: Bonnardel J, Guillia...
-
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2tcPIjn via IFTTT
-
Abstract: Epidermolytic ichthyosis (EI) is a rare disorder of cornification caused by mutations in KRT1 and KRT10, encoding two suprabasal e...
-
Bloomberg Celgene Settles Whistle-Blower Fraud Suit for $280 Million Bloomberg Even after the FDA approved Thalomid for multiple myelo...
-
Related Articles Chinese version of the Constant-Murley questionnaire for shoulder pain and disability: a reliability and validation ...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου