Genetic polymorphisms of glutathione S-transferase M1 and T1, and evaluation of oxidative stress in patients with non-small cell lung cancer

Abstract Various genetic polymorphisms have been linked to lung cancer susceptibility and survival outcomes. Vitamin D (VD) regulates cell proliferation and differentiation, inhibits tumor growth and induces apoptosis. Observations from several previous studies including our own suggest that genetic polymorphisms in the VD pathway may be associated with lung cancer risk. The aim of this study is to assess if genetic polymorphisms in the VD pathway are associated with the prognosis of non-small cell lung cancer (NSCLC). Nine single nucleotide polymorphisms (SNPs) in five genes in the VD pathway were genotyped with the TaqMan assays in 542 patients with primary NSCLC, and the relationships between these SNPs and overall survival were evaluated. We found that SNP rs10741657 in the CYP2R1 gene was associated with the prognosis of NSCLC, especially in elderly patients and not being treated with chemotherapy. Some of the VD pathway-related genetic polymorphisms may influence the prognosis of NSCLC. More research is needed to further confirm the finding and test if VD supplements can be used for NSCLC treatment.

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Genetic polymorphisms and haplotypes of BRCA1 gene associated with quality of life and survival among patients with non-small-cell lung cancer

Quality of Life Research ◽

10.1007/s11136-020-02509-2 ◽

2020 ◽

Vol 29 (10) ◽

pp. 2631-2640

Author(s):

Tong Su ◽

Hao Sun ◽

Xiaofang Lu ◽

Chen He ◽

Lei Xiao ◽

...

Keyword(s):

Quality Of Life ◽

Lung Cancer ◽

Small Cell Lung Cancer ◽

Genetic Polymorphisms ◽

Cell Lung Cancer ◽

Brca1 Gene ◽

Small Cell ◽

Small Cell Lung

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Hypoxia-Induced Cisplatin Resistance in Non-Small Cell Lung Cancer Cells Is Mediated by HIF-1α and Mutant p53 and Can Be Overcome by Induction of Oxidative Stress

Cancers ◽

10.3390/cancers10040126 ◽

2018 ◽

Vol 10 (4) ◽

pp. 126 ◽

Cited By ~ 24

Author(s):

Christophe Deben ◽

Vanessa Deschoolmeester ◽

Jorrit De Waele ◽

Julie Jacobs ◽

Jolien Van den Bossche ◽

...

Keyword(s):

Oxidative Stress ◽

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Cells ◽

Cell Lung Cancer ◽

Cisplatin Resistance ◽

Small Cell ◽

Mutant P53 ◽

Small Cell Lung ◽

Hypoxic Conditions

The compound APR-246 (PRIMA-1MET) is a known reactivator of (mutant) p53 and inducer of oxidative stress which can sensitize cancer cells to platinum-based chemotherapeutics. However, the effect of a hypoxic tumor environment has been largely overlooked in this interaction. This study focusses on the role of hypoxia-inducible factor-1α (HIF-1α) and the p53 tumor suppressor protein in hypoxia-induced cisplatin resistance in non-small cell lung cancer (NSCLC) cells and the potential of APR-246 to overcome this resistance. We observed that hypoxia-induced cisplatin resistance only occurred in the p53 mutant NCI-H2228Q331* cell line, and not in the wild type A549 and mutant NCI-H1975R273H cell lines. Cisplatin reduced HIF-1α protein levels in NCI-H2228Q331* cells, leading to a shift in expression from HIF-1α-dependent to p53-dependent transcription targets under hypoxia. APR-246 was able to overcome hypoxia-induced cisplatin resistance in NCI-H2228Q331* cells in a synergistic manner without affecting mutant p53Q331* transcriptional activity, but significantly depleting total glutathione levels more efficiently under hypoxic conditions. Synergism was dependent on the presence of mutant p53Q331* and the induction of reactive oxygen species, with depletion of one or the other leading to loss of synergism. Our data further support the rationale of combining APR-246 with cisplatin in NSCLC, since their synergistic interaction is retained or enforced under hypoxic conditions in the presence of mutant p53.

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GSTP1-catalyzed PKM2 S-Glutathionylation Regulates Glycolysis in Non-small Cell Lung Cancer and is Attenuated with a Clinically Relevant inhibitor of Glutathione-S-transferase P

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2017.10.158 ◽

2017 ◽

Vol 112 ◽

pp. 104-105

Author(s):

Jos van der Velden ◽

Matthew Kinsey ◽

Shibiao Chia ◽

Karolyn Lahue ◽

Xi Qian ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Glutathione S Transferase

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Association of genetic polymorphisms of CXCL12/SDF1 gene and its receptor, CXCR4, to the susceptibility and prognosis of non-small cell lung cancer

Lung Cancer ◽

10.1016/j.lungcan.2010.12.011 ◽

2011 ◽

Vol 73 (2) ◽

pp. 147-152 ◽

Cited By ~ 19

Author(s):

Yao-Ling Lee ◽

Wu-Hsien Kuo ◽

Chiao-Wen Lin ◽

Wei Chen ◽

Wei-Erh Cheng ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Genetic Polymorphisms ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung

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A Study on Cytotoxic and Apoptotic Potential of a Triterpenoid Saponin (3-O-α-L-Arabinosyl Oleanolic Acid) Isolated fromSchumacheria castaneifoliaVahl in Human Non-Small-Cell Lung Cancer (NCI-H292) Cells

BioMed Research International ◽

10.1155/2017/9854083 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Sameera R. Samarakoon ◽

Meran K. Ediriweera ◽

Chukwumaobim Daniel Uzochukwuwulu Nwokwu ◽

Chamara Janaka Bandara ◽

Kamani H. Tennekoon ◽

...

Keyword(s):

Oxidative Stress ◽

Lung Cancer ◽

Small Cell Lung Cancer ◽

Oleanolic Acid ◽

Cell Lung Cancer ◽

Caspase 3 ◽

Small Cell ◽

Normal Lung ◽

Small Cell Lung ◽

Cytotoxic Effects

Lung cancer is the major cause of cancer death among men. A number of natural compounds have proven to be useful in the treatmet of lung cancer. This study was aimed to determine cytotoxic and apoptotoic effects of a natural compound 3-O-α-L-arabinosyl oleanolic acid (3-O-L-AO) isolated fromSchumacheria castaneifoliain non-small-cell lung cancer (NCI-H292) cells. Cytotoxic effects of 3-O-L-AO were determined by Sulforhodamine B (SRB) assay and apoptotic effects were tested by evaluating (a) apoptotsis related morphological changes, (b) caspase 3/7 activity, and (c) expression ofBax, p53, and survivingenes. Oxidative stress markers (reactive oxygen species (ROS), glutathione-S-transferase (GST), and glutathione (GSH)) were also analysed in 3-O-L-AO treated NCI-H292 cells. 3-O-L-AO exerted potent cytotoxic effects in NCI-H292 cells while being less cytotoxic to normal lung (MRC-5) cells. Exposure to 3-O-L-AO caused upregulation ofBaxandp53and downregulation ofsurvivinin NCI-H292 cells. Activation of caspase 3/7 and morphological features related to apoptosis further confirmed 3-O-L-AO induced apoptosis. Furthermore, elevated ROS and GST levels and decreased GSH levels suggested 3-O-L-AO can induce apoptosis, possibly causing oxidative stress in NCI-H292 cells. Overall results suggest that 3-O-L-AO can be considered as an effective anticancer agent for the treatment of lung cancer.

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