Particularly, genetic polymorphisms in NAD(P)H-quinone oxidoreductase (NQO1), cytochrome P450 (CYP)1A1, myeloperoxidase (MPO), glutathione-S-transferase (GST)P1, GSTT1, and GSTM1, and have been suspected to affect lung cancer risk.
The risk of lung and urinary bladder cancers was reported to be increased in individuals who carried high risk genotypes in either cytochrome P450 (CYP)1A1, CYP2E1 or glutathione S-transferase (GST)M1, and the combined genotype of both CYP1A1 and GSTM1 enzymes have an enhanced tendency of risk to lung cancer more significantly.
To investigate the relationship between GST genotypes and lung cancer risk in Xuan Wei County, we analyzed GSTM1 and GSTT1 genotypes in a population-based case-control study.
Although the susceptibility to lung cancer showing gene deletion for GST mu isoform in non-smoking group is not significantly different from that in smoking group, a great number of individuals with gene deletion was found among cancer patients who are less than 50 years old.
Based on this strategy, a novel piperlongumine analog (PL-13) bearing a para-trifluoromethyl group and an α-chlorine on its aromatic and lactam rings, respectively, surfaced as a promising GST inhibitor, thereby overcoming cisplatin resistance in lung cancer A549 cells.
Among the related proteins, GST-π may be useful for the prediction of the intrinsic resistance to cisplatin, whereas TopoIIα may be useful to predict resistance to doxorubicin and VP-16 in human lung cancer cell lines.
The relationships between smoking and the expression of glutathione S-transferase (GST*) isozymes GSTM1-1, GSTM3-3, GSTP1-1 and GSTA1-1/2-2 (GSTA1/2), or between smoking and activities of epoxide hydrolase (EH) and aryl hydrocarbon hydroxylase (AHH) were investigated in lung samples from 27 patients with lung cancer and 11 control patients by immunoblot analysis and enzyme assays.
We found that high expressions of both GST-M2 and CCN2 are correlated with favorable survival of patients with lung cancer when compared with similar patients without GST-M2 or CCN2 expression.
Then, co-immunoprecipitation (Co-IP) and GST-pull down assays indicated that the candidate protein-SLC27A4 directly interacts with ATG4B in lung cancer cell lines.
The association between ITC and cancer, and its modification by GST status, is most consistent for lung cancer and appears to be strongest among current smokers.
Treatment with ferulenol significantly increased the rate of lipid peroxidation and decrease enzymatic (CAT and GST) and non-enzymatic (GSH) anti-oxidants in benzo[a]pyrene induced lung cancer.
In order to better understand the role of this enzyme in chemo- and/or radioresistance of lung cancer cells, we examined whether introduction of GST-pi cDNA into a chemo- and radiosensitive lung cancer cell line altered its sensitivities to various chemotherapeutic agents and/or ionizing radiation, which are often used in the management of lung cancers.
The authors evaluated the promoter methylation of GST-M2 in lung cancer cells after treatment with the DNA methyltransferase (DNMT) inhibitor 5'-aza-2'-deoxycytidine (5'-aza-dC).
The presence of glutathione S-transferase (GST) pi1 (GSTP1) or multidrug resistance gene 1 (MDR1) promoter methylation in lung cancer was studied for the first time to the authors' knowledge; and, to date, the clinical significance of methylation is not clear.
A new class of human GST inhibitors has been identified via rational design approach; we report their discovery, synthesis, inhibitory activity, and synergetic effect in combination with cisplatin against A549 lung cancer cell line.
These results suggest that GST-pi gene expression is associated with chronic exposure to platinum drugs in lung cancer and/or the stress response to xenobiotics.
GST pi was also variably expressed in human tumors, with the lowest relative levels occurring in lymphoma and breast cancer and the highest levels found in lung cancer and head and neck tumors.
The finding that GST pi mRNA was overexpressed after irradiation was validated by investigations on a human lung carcinoma cell line (LXF 289) on the mRNA and protein level.
Uninvolved lung tissue was obtained from 35 patients with lung carcinoma and 43 control patients and assayed for GST-mu activity with TSO, for the presence of the GST-mu gene product with an immunological assay, and for the GST-mu gene with Southern blotting.