Cytoprotective and regulatory functions of glutathione S-transferases in cancer cell proliferation and cell death

GSTP1 belongs to the GSTs family, a group of enzymes involved in detoxification of exogenous substances and it also plays an important role in cell cycle regulation. Its dysregulation correlates with a large variety of tumors, in particular with prostate cancer. We investigated GSTP1 methylation status with methylation specific PCR (MS-PCR) in prostate cancer (PCa) and in benign tissue of 56 prostatectomies. We also performed immunohistochemistry (IHC) so as to correlate gene methylation with gene silencing. GSTP1 appears methylated in PCa and not in healthy tissue; IHC confirmed that methylation leads to protein underexpression (p < 0.001). GSTP1 is highly expressed in basal cell layer and luminal cells in benign glands while in prostatic intraepithelial neoplasia (PIN) it stains only basal cell layer, whereas PCa glands are completely negative. We demonstrated that methylation leads to underexpression of GSTP1. The progressive loss of GSTP1 expression from healthy glands to PIN and to PCa glands underlines its involvement in early carcinogenesis.

show abstract

“…Therefore, GST plays an important role in cancer cell proliferation and death thanks to its cytoprotective and regulatory functions [2]. …”

Section: Introductionmentioning

confidence: 99%

GSTP1Methylation and Protein Expression in Prostate Cancer: Diagnostic Implications

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Previous studies investigating cancer development have examined various genes, including oncogenes, tumor suppressor genes, DNA repair genes, and genes encoding phase I and II enzymes (9)(10)(11)(12). GSH levels have been shown to be elevated in numerous types of human cancer, including bone marrow (13), breast (14,15) and lung (16,17).…”

Section: Introductionmentioning

confidence: 99%

Involvement of glutathione and glutathione metabolizing enzymes in human colorectal cancer cell lines and tissues

Kim

Zhang

Han

et al. 2015

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…Currently, growing evidence indicates that GSTs enzyme determines the cytotoxicity of a variety of chemotherapeutic agents (Kabler et al, 2009;Sharma et al, 2011), especially the platinum drugs (Fuertes et al, 2003). Five subclasses of the GSTs superfamily exist, and glutathione S-transferase P1 (GSTP1) is the most abundant GSTs isoform in the lung (Singh et al, 2015;Ou et al, 2015). GSTP1, directly participating in the detoxification of platinum compounds is an important mediator of both intrinsic and acquired resistance to platinum (Parker et al, 2011;De Luca et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Association of GSTP1 and RRM1 Polymorphisms with the Response and Toxicity of Gemcitabine-cisplatin Combination Chemotherapy in Chinese Patients with Non-small Cell Lung Cancer

Yuan

Zhou²,

Liu³

et al. 2015

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1) were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) were correlated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivity and clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatin regimens. Materials and Methods: DNA sequencing was used to evaluate genetic polymorphisms of GSTP1 Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinical response was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessed by 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents). Results: There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequency distribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive group had higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the joint detection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A + high effective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicity showed no correlation with the genotypes between two groups (p>0.05). Conclusions: Compared with single detection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may be more helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy. Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict the response and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.

show abstract

Cytoprotective and regulatory functions of glutathione S-transferases in cancer cell proliferation and cell death

Cited by 115 publications

References 110 publications

GSTP1Methylation and Protein Expression in Prostate Cancer: Diagnostic Implications

GSTP1Methylation and Protein Expression in Prostate Cancer: Diagnostic Implications

Involvement of glutathione and glutathione metabolizing enzymes in human colorectal cancer cell lines and tissues

Association of GSTP1 and RRM1 Polymorphisms with the Response and Toxicity of Gemcitabine-cisplatin Combination Chemotherapy in Chinese Patients with Non-small Cell Lung Cancer

Contact Info

Product

Resources

About