Metabolic oxidative stress induced by a combination of 2-DG and 6-AN enhances radiation damage selectively in malignant cells via non-coordinated expression of antioxidant enzymes.

Abstract:

:Our earlier studies have shown that simultaneous inhibition of glycolysis and pentose phosphate pathway using 2-deoxy-d-glucose (2-DG, an inhibitor of glycolysis) and 6-aminonicotinamide (6-AN, an inhibitor of pentose phosphate pathway) lead to metabolic oxidative stress (MOS), resulting in radiosensitization in malignant cells. Present study was carried out to investigate the effects of 2-DG and 6-AN on intricately regulated endogenous antioxidant defense against MOS during radiosensitization by this combination. Two human tumor cell lines {Head and Neck Squamous carcinoma (KB) and Glioma (BMG-1)} and one non-malignantly transformed cell line (human embryonic kidney, HEK) were used in this study. The presence of 2-DG and 6-AN (added just before irradiation) for 4h, significantly decreased the clonogenicity and metabolic viability of KB and BMG-1 cell lines, while no significant change was seen in HEK cells. Accumulation of ROS was observed only in malignant cell lines, which displayed a compromised redox status evident from enhanced NADP(+)/NADPH and GSSG/GSH ratios and a concomitant decrease in glutathione reductase level and activity at 24h following treatment. The levels and activities of Cu, Zn-SOD and Mn-SOD increased with MOS and were accompanied by a decreased GPx and unaltered catalase activity and level. These results suggest that non-coordinated expression of antioxidant defense, besides compromised redox status, led to selective radiosensitization in the malignant cells.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Sharma PK,Bhardwaj R,Dwarakanath BS,Varshney R

doi

10.1016/j.canlet.2010.02.021

subject

Has Abstract

pub_date

2010-09-28 00:00:00

pages

154-66

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(10)00122-9

journal_volume

295

pub_type

杂志文章
  • Heat shock protein expression in human tumours grown in severe combined immunodeficient mice.

    abstract::The constitutional expression of heat shock proteins (HSP) 27, 70 and 90 in human breast, colon and ovarian cancer cells transplanted into severe combined immunodeficient (SCID) mice was evaluated. In addition their induced expression under chemotherapeutic stress was analyzed. The oestrogen receptor positive breast c...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(00)00601-7

    authors: Katoh M,Koninkx J,Schumacher U

    更新日期:2000-12-08 00:00:00

  • Enhancing effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) on cell proliferation and lipid peroxidation in the rat gastric mucosa.

    abstract::The influence of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, a mutagen in chlorinated water, on cell proliferation and lipid peroxidation in the glandular stomach mucosa was investigated in male 4-week-old Wistar rats. Animals were given 50 p.p.m., 25 p.p.m., 12.5 p.p.m., 6.25 p.p.m. or 0 p.p.m. of MX soluti...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(94)90268-2

    authors: Nishikawa A,Kinae N,Furukawa F,Mitsui M,Enami T,Hasegawa T,Takahashi M

    更新日期:1994-10-14 00:00:00

  • Expression of cyclooxygenase-2 in colorectal adenocarcinoma is associated with p53 accumulation and hdm2 overexpression.

    abstract::Elevated cyclooxygenase-2 (COX-2) expression has been observed in various types of cancer. Induction of COX-2 expression has been reported to increase invasiveness and angiogenesis of tumours. While COX-2 overexpression has been repeatedly proven to promote tumor growth, little is known about what initiates its induct...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2005.03.023

    authors: Cressey R,Pimpa S,Tontrong W,Watananupong O,Leartprasertsuke N

    更新日期:2006-02-28 00:00:00

  • Sulofenur cytotoxicity and changes in cytosolic calcium and mitochondrial membrane potential in human colon adenocarcinoma cell lines.

    abstract::Sulofenur treatment (12.5 microM-1 mM) of colon adenocarcinoma cell lines resulted in dose- and time-dependent cell killing. LYc5 cells were viable longer than GC3/c1 cells. Each concentration resulted in elevation of cytosolic calcium [Ca2+]i) for both cell lines. At lower doses, elevation was delayed for LYc5 cells....

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(94)03607-k

    authors: Phelps PC,Jain PT,Berezesky IK,Boder GB,Trump BF

    更新日期:1995-01-06 00:00:00

  • The role of membrane transporters in drug delivery to brain tumors.

    abstract::Most brain tumors are highly resistant to chemotherapy because many chemotherapeutic drugs poorly cross the blood-brain barrier, the blood-cerebrospinal-fluid barrier, and the plasma membrane of the tumor cells. This restricted drug delivery is largely due to the presence of integral plasma membrane proteins belonging...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2006.12.023

    authors: Nies AT

    更新日期:2007-08-28 00:00:00

  • Expression of p53 protein related to smoking and alcoholic beverage drinking habits in patients with esophageal cancers.

    abstract::In esophageal squamous cell carcinoma (SCC), we used immunohistochemical analysis to further elucidate the correlation of p53 protein expression with clinicopathological factors, as well as with risk factors, such as tobacco smoking, alcohol consumption and a family history of cancer, using odds ratios (ORs). The expr...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(01)00461-x

    authors: Kato H,Yoshikawa M,Miyazaki T,Nakajima M,Fukai Y,Tajima K,Masuda N,Tsukada K,Fukuda T,Nakajima T,Kuwano H

    更新日期:2001-06-10 00:00:00

  • An novel inhibitor of TGF-β type I receptor, IN-1130, blocks breast cancer lung metastasis through inhibition of epithelial-mesenchymal transition.

    abstract::TGF-β signaling plays an important role in breast cancer progression and metastasis. Epithelial-mesenchymal transition (EMT) is an important step in the progression of solid tumors to metastatic disease. We previously reported that IN-1130, a novel transforming growth factor-β type I receptor kinase (ALK5) inhibitor, ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2014.05.006

    authors: Park CY,Min KN,Son JY,Park SY,Nam JS,Kim DK,Sheen YY

    更新日期:2014-08-28 00:00:00

  • Effects of the synthetic trypsin inhibitor camostate on the development of N-nitrosobis(2-oxopropyl)amine-induced pancreatic lesions in hamsters.

    abstract::Trypsin inhibitors have been shown to promote pancreatic growth as well as the development of pancreatic tumours in rats. The present study was carried out to examine the effects of the synthetic trypsin inhibitor camostate on the growth of the pancreas and on the development of pancreatic preneoplastic and neoplastic...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(91)90115-x

    authors: Meijers M,van Garderen-Hoetmer A,Lamers CB,Rovati LC,Jansen JB,Woutersen RA

    更新日期:1991-12-01 00:00:00

  • Nitrotyrosine in esophageal squamous cell carcinoma and relevance to p53 expression.

    abstract::We have examined the expression of nitrotyrosine, a marker of peroxynitrite formation, in 55 esophageal cancers by immunohistochemistry. Nitrotyrosine was detected in 21 of 55 (38.2%) esophageal cancers. Comparison of nitrotyrosine expression and the pathological findings showed that there was a significant associatio...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(00)00358-x

    authors: Kato H,Miyazaki T,Yoshikawa M,Nakajima M,Fukai Y,Tajima K,Masuda N,Tsutsumi S,Tsukada K,Nakajima T,Kuwano H

    更新日期:2000-05-29 00:00:00

  • Frequent loss of heterozygosity on multiple chromosomes in Chinese esophageal squamous cell carcinomas.

    abstract::Analysis of the loss of heterozygosity (LOH) detected by polymerase chain reaction techniques using 18 polymorphic markers localized to chromosomes 3p, 5, 17, and 18q in 40 Hong Kong Chinese esophageal squamous cell carcinoma (ESC) patients showed that multiple alterations on several chromosomes are involved in ESC de...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(01)00577-8

    authors: Ko JM,Wong CP,Tang CM,Lau KW,Lung ML

    更新日期:2001-09-20 00:00:00

  • Staurosporine-induced G(1) arrest in cancer cells depends on an intact pRB but is independent of p16 status.

    abstract::Staurosporine and its derivative 7-hydroxystaurosporine are protein kinase inhibitors that are being considered for treatments of cancers. Several recent studies have shown that cells with defective pRB protein are resistant to the G(1) cell cycle-inhibiting effects of staurosporine compounds. In this study, we examin...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(02)00101-5

    authors: Zhou W,Lin Y,Wersto R,Chrest J,Gabrielson E

    更新日期:2002-09-08 00:00:00

  • Antitumor activity of a novel nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosylcytosine (CNDAC) against murine and human tumors.

    abstract::The antitumor effects of 2'-C-cyano-2'-deoxy-1-beta-D- arabinofuranosylcytosine (CN-DAC), a synthetic 1-beta-D-arabinofuranosyl-cytosine (ara-C) derivative, were examined and compared with that of ara-C in murine tumors and in various human tumors using three different chemosensitivity tests. CNDAC extended the life s...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(92)90024-p

    authors: Tanaka M,Matsuda A,Terao T,Sasaki T

    更新日期:1992-05-30 00:00:00

  • Transductional and transcriptional targeting of cancer cells using genetically engineered viral vectors.

    abstract::Gene delivery vectors, including adenovirus (Ad) and adeno-associated virus (AAV), are inefficient and non-selective for cancer due to low levels of viral receptors with high levels on other tissues, including liver. We tested Ads and AAVs with the SIGYPLP-targeting peptide inserted into virus capsids for transduction...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2003.07.003

    authors: Nicklin SA,Dishart KL,Buening H,Reynolds PN,Hallek M,Nemerow GR,Von Seggern DJ,Baker AH

    更新日期:2003-11-25 00:00:00

  • Tumor initiating activities of 1-nitropyrene and its nitrated products in SENCAR mice.

    abstract::The environmental mutagens, 1-nitropyrene, 1,3-dinitropyrene, 1,6-dinitropyrene and 1,8-dinitropyrene were evaluated for their ability to initiate skin tumors in male and female SENCAR mice. 1-Nitropyrene (greater than 99.5% purity) did not induce papilloma formation over a dose range of 0-3.0 mg/mouse after 30 weeks ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(84)90055-7

    authors: Nesnow S,Triplett LL,Slaga TJ

    更新日期:1984-05-01 00:00:00

  • Exposure to low dose ionising radiation: Molecular and clinical consequences.

    abstract::This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HR...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2013.12.015

    authors: Martin LM,Marples B,Lynch TH,Hollywood D,Marignol L

    更新日期:2014-07-10 00:00:00

  • Long noncoding RNAs as potential biomarkers in gastric cancer: Opportunities and challenges.

    abstract::Gastric cancer (GC) is a major threat to human health, and its prognosis is poor due to the lack of appropriate biomarkers. LncRNAs are a group of non-protein-coding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. LncRNAs play essential roles in GC initiation and development in ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2015.11.011

    authors: Yang Z,Guo X,Li G,Shi Y,Li L

    更新日期:2016-02-01 00:00:00

  • Nitrated T helper cell epitopes enhance the immunogenicity of HER2 vaccine and induce anti-tumor immunity.

    abstract::Human epidermal growth factor receptor 2 (HER2) is an attractive target for cancer vaccine. However, autoimmune tolerance prevents vaccines based on HER2 protein from inducing long-lasting, highly effective anti-tumor immunity. In this study, we proved that the introduction of p-nitrophenylalanine in the universal T c...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2018.05.021

    authors: Tian H,He Y,Song X,Jiang L,Luo J,Xu Y,Zhang W,Gao X,Yao W

    更新日期:2018-08-28 00:00:00

  • Milk exosomes - Natural nanoparticles for siRNA delivery.

    abstract::Gene-silencing with targeted siRNAs has great potential as a therapeutic approach for various diseases including cancer. However, intracellular delivery of siRNA is challenging. We used bovine milk exosomes as a novel system for siRNA delivery. First, we demonstrated that exosomes can deliver endogenous RNA payloads i...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2019.02.011

    authors: Aqil F,Munagala R,Jeyabalan J,Agrawal AK,Kyakulaga AH,Wilcher SA,Gupta RC

    更新日期:2019-05-01 00:00:00

  • Nicotine and cotinine in breast fluid.

    abstract::Breast fluid which bathes the mammary ductal epithelium may contain tumorogenic components. In view of the number of tobacco components inhaled during smoking, it was of interest whether nicotine and its metabolites were present in this fluid. Fluid was obtained from the nipple from menstruating women who were smokers...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(79)80042-7

    authors: Hill P,Wynder EL

    更新日期:1979-04-01 00:00:00

  • Targeting the p53-MDM2 pathway for neuroblastoma therapy: Rays of hope.

    abstract::Despite being the subject of extensive research and clinical trials, neuroblastoma remains a major therapeutic challenge in pediatric oncology. The p53 protein is a central safeguard that protects cells against genome instability and malignant transformation. Mutated TP53 (the gene encoding p53) is implicated in many ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2020.09.023

    authors: Zafar A,Wang W,Liu G,Xian W,McKeon F,Zhou J,Zhang R

    更新日期:2021-01-01 00:00:00

  • A glutathione S-transferase inducer from papaya: rapid screening, identification and structure-activity relationship of isothiocyanates.

    abstract::We have developed a simple system for rapid detection and measurement of glutathione S-transferase placental form (GSTP1) that detoxify polycyclic aromatic hydrocarbons using the cultured rat normal liver epithelial cell line, (RL34) cells. Survey of fruit extracts for GST inducing ability identified both papaya and a...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(00)00487-0

    authors: Nakamura Y,Morimitsu Y,Uzu T,Ohigashi H,Murakami A,Naito Y,Nakagawa Y,Osawa T,Uchida K

    更新日期:2000-09-01 00:00:00

  • Involvement of the polyamine pathway in breast cancer progression.

    abstract::These experiments were designed to test the role of the polyamine pathway in breast cancer progression utilizing an experimental system based on the development of ovary-independent rat mammary tumors and their sequential transplantation into syngeneic hosts. Three key enzymes involved in the PA biosynthetic/catabolic...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(95)03763-m

    authors: Manni A,Grove R,Kunselman S,Aldaz CM

    更新日期:1995-05-25 00:00:00

  • Postnatal efficacy of Momordica charantia peel, pulp, seed and whole fruit extract in the detoxication pathway of suckling neonates and lactating mice.

    abstract::The present study evaluates the postnatal efficacy of Momordica charantia peel, pulp, seed and whole fruit extract via assessing the modulation in the biotransformation system enzymes of suckling neonates and lactating mice. The peel, seed or whole fruit extract of Momordica (100 microl/animal/day) independently induc...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(97)00381-9

    authors: Singh A,Singh SP,Bamezai R

    更新日期:1998-01-09 00:00:00

  • Fibronectin acts as a molecular switch to determine SPARC function in pancreatic cancer.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest of all solid tumours and more effective therapy is urgently needed. The stroma is thought to play a critical role in tumour development and metastasis, and high stromal expression of the matricellular protein SPARC has been robustly associated with poor p...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2020.02.031

    authors: Munasinghe A,Malik K,Mohamedi F,Moaraf S,Kocher H,Jones L,Hill NJ

    更新日期:2020-05-01 00:00:00

  • Genetic and epigenetic analysis of the TIMP-3 gene in ovarian cancer.

    abstract::Chromosome 22q shows a high frequency of loss of heterozygosity (LOH) in ovarian cancers suggesting the existence of one or more important tumor suppressor genes (TSGs). The tissue inhibitor of metalloproteinase-3 (TIMP-3) is a plausible TSG candidate since it is often encompassed within these regions of LOH. TIMP-3 h...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2006.03.024

    authors: Liu MC,Choong DY,Hooi CS,Williams LH,Campbell IG

    更新日期:2007-03-08 00:00:00

  • Synergistic cytotoxic effect of human recombinant tumor necrosis factor alpha combined with dihydroambazone.

    abstract::Dihydroambazone (DHA) is a water-soluble derivative of the experimental anticancer drug ambazone. In vitro, a combination of DHA and human recombinant tumor necrosis factor alpha (TNF) exerted a strong synergism of cytotoxicity against both mouse melanoma B16K cells and the TNF-sensitive mouse fibroblast line L-M (S)....

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(90)90032-s

    authors: Baumgart J,Gase K,Schulze W,Suehnel J,Gutsche W,Behnke D

    更新日期:1990-11-05 00:00:00

  • MicroRNA-1 suppresses glioblastoma in preclinical models by targeting fibronectin.

    abstract::Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We found that miR-1 is expressed at relatively low levels in brain cancer patients...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2019.08.021

    authors: Yang CH,Wang Y,Sims M,Cai C,Pfeffer LM

    更新日期:2019-11-28 00:00:00

  • Mapping of the methylation pattern of the MUC2 promoter in pancreatic cancer cell lines, using bisulfite genomic sequencing.

    abstract::Expression of the MUC2 gene is controlled by the methylation of CpG sites in the promoter region, but the detailed methylation status of this region has yet to be reported. We have mapped the complete methylation status of the MUC2 promoter from position -1989 to position +288 upstream, a region that contains 59 CpG s...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2004.11.058

    authors: Hamada T,Goto M,Tsutsumida H,Nomoto M,Higashi M,Sugai T,Nakamura S,Yonezawa S

    更新日期:2005-09-28 00:00:00

  • Effect of continuous light on the incidence of 9,10-dimethyl-1,2-benzanthracene induced mammary tumors in female Holtzman rats.

    abstract::The pineal has been recently implicated in mammary tumorigenesis. Effect of physiological pinealectomy brought about by subjecting female Holtzman rats to permanent lighting (24 h/day) from birth was studied on the incidence of 9,10-dimethyl-1,2-benzanthracene (DMBA) induced mammary tumors. The incidence of adenocarci...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(82)90012-x

    authors: Kothari LS,Shah PN,Mhatre MC

    更新日期:1982-09-01 00:00:00

  • DNA demethylation by 5-aza-2-deoxycytidine treatment abrogates 17 beta-estradiol-induced cell growth and restores expression of DNA repair genes in human breast cancer cells.

    abstract::Prolonged exposure to elevated levels of estrogen is a risk factor for breast cancer. Though increased cell growth and loss of DNA repair capacity is one of the proposed mechanisms for estrogen-induced cancers, the mechanism through which estrogen induces cell growth and decreases DNA repair capacity is not clear. DNA...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2011.10.022

    authors: Singh KP,Treas J,Tyagi T,Gao W

    更新日期:2012-03-01 00:00:00