Nitrogen mustard up-regulates Bcl-2 and GSH and increases NTP and PCr in HT-29 colon cancer cells
AuthorBoddie Jr., A. W.
Constantinou, Andreas I.
SourceBritish journal of cancer
Google Scholar check
MetadataShow full item record
We hypothesized that unexplained increases in nucleoside triphosphates (NTP) observed by 31P magnetic resonance spectroscopy (MRS) after treatment of tumours by DNA-damaging agents were related to chemotherapy-induced up-regulation of the bcl-2 gene and DNA damage prevention and repair processes. To test this hypothesis, we treated HT-29 cells with 10-4 M nitrogen mustard (HN2) and performed sequential perchloric acid extractions in replicate over 0-18 h. By reference to an internal standard (methylene diphosphonic acid), absolute changes in 31P-detectable high-energy phosphates in these extracts were determined and correlated with changes in bcl-2 protein levels, cell viability, cell cycle, apoptosis and total cellular glutathione (GSH) (an important defence against DNA damage from alkylating agents). After HN2 administration, bcl-2 protein levels in the HT-29 cell line rose at 2 h. Cell viability declined to 25% within 18 h, but apoptosis measured using fluorescence techniques remained in the 1-4% range. Increased cell division was noted at 4 h. Two high-energy interconvertible phosphates, NTP (P ≤ 0.006) and phosphocreatine (PCr) (P ≤ 0.0002), increased at 2 h concurrently with increased levels of bcl-2 protein and glutathione. This study demonstrates that bcl-2 and glutathione are up-regulated by HN2 and links this to a previously unexplained 31P MRS phenomenon: increased NTP after chemotherapy.
Showing items related by title, author, creator and subject.
Binding free energies and free energy components from molecular dynamics and Poisson-Boltzmann calculations. Application to amino acid recognition by aspartyl-tRNA synthetase Archontis, Georgios Z.; Simonson, T.; Karplus, M. (2001)Specific amino acid binding by aminoacyl-tRNA synthetases (aaRS) is necessary for correct translation of the genetic code. Engineering a modified specificity into aminoacyl-tRNA synthetases has been proposed as a means to ...
Molecular investigation of distal renal tubular acidosis in Tunisia, evidence for founder mutations Nagara, Majdi; Voskarides, Konstantinos; Nouira, S.; Ben Halim, N.; Kefi Ben Atig, Rym; Aloulou, Hajer; Romdhane, L.; Ben Abdallah, R.; Ben Rhouma, F.; Aissa, K.; Boughamoura, L.; Kammoun, T.; Azzouz, H.; Abroug, S.; Ben Turkia, H.; Ayadi, A.; Mrad, R.; Chabchoub, I.; Hachicha, M.; Chemli, J.; Constantinou-Deltas, Constantinos D.; Abdelhak, S. (2014)BACKGROUND: Distal renal tubular acidosis (dRTA) is a rare genetic disease caused by mutations in different genes involved in the secretion of H+ ions in the intercalated cells of the collecting duct. Both autosomal dominant ...
In vivo high-resolution magic angle spinning magnetic and electron paramagnetic resonance spectroscopic analysis of mitochondria-targeted peptide in Drosophila melanogaster with trauma-induced thoracic injury Constantinou, Constantina; Apidianakis, Yiorgos; Psychogios, N.; Righi, V.; Mindrinos, M. N.; Khan, N.; Swartz, H. M.; Szeto, H. H.; Tompkins, R. G.; Rahme, L. G.; Aria Tzika, A. (2016)Trauma is the most common cause of mortality among individuals aged between 1 and 44 years and the third leading cause of mortality overall in the US. In this study, we examined the effects of trauma on the expression of ...