Rabbit Anti-Human GSTP1 (a.a. 1-210) Polyclonal antibody

INTRODUCTION: Numerous studies have been investigated to understand the association between glutathione S-transferase P1 (GSTP1) polymorphism and risk of head and neck cancer (HNC) but yielded contradictory results, and no studies could confirm polymorphism in GSTP1 and that tobacco usage increases the risk of HNCs. Therefore, this study aimed to understand the association of GSTP1 Ile105Val polymorphism with or without tobacco usage in carcinogenesis and clinicopathological characteristics of patients with HNC. MATERIALS AND METHODS: Binary logistic regression analysis was performed to predict HNC risk with tobacco use and GSTP1 genotyping. Five predictor variables such as gender, age, tobacco usage, familial, and GSTP1 genotypes were included in the model. RESULTS: The results of the logistic regression analysis show that the full model which considered all the five independent variables together was statistically significant, log-likelihood = -111.820, and all slopes are zero: G = 74.297, degree of freedom (DF) = 5, P = 0.000. The strongest predictor in this model is tobacco usage (odds ratio = Z = -5.16, P = 0.000). CONCLUSION: The study concludes that multiple logistic regression analysis model could predict the risk factors in case-control studies where control samples are compromised.

Background Glioblastoma (GBM) is a universally lethal tumor with frequently overexpressed or mutated epidermal growth factor receptor (EGFR). NADPH quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase Pi 1 (GSTP1) are commonly upregulated in GBM. NQO1 and GSTP1 decrease the formation of reactive oxygen species (ROS), which mediates the oxidative stress and promotes GBM cell proliferation. Methods High-throughput screen was used for agents selectively active against GBM cells with EGFRvIII mutations. Co-crystal structures were revealed molecular details of target recognition. Pharmacological and gene knockdown/overexpression approaches were used to investigate the oxidative stress in vitro and in vivo. Results We identified a small molecular inhibitor, "MNPC," that binds to both NQO1 and GSTP1 with high affinity and selectivity. MNPC inhibits NQO1 and GSTP1 enzymes and induces apoptosis in GBM, specifically inhibiting the growth of cell lines and primary GBM bearing the EGFRvIII mutation. Co-crystal structures between MNPC and NQO1, and molecular docking of MNPC with GSTP1 reveal that it binds the active sites and acts as a potent dual inhibitor. Inactivation of both NQO1 and GSTP1 with siRNA or MNPC results in imbalanced redox homeostasis, leading to apoptosis and mitigated cancer proliferation in vitro and in vivo. Conclusions Thus, MNPC, a dual inhibitor for both NQO1 and GSTP1, provides a novel lead compound for treating GBM via the exploitation of specific vulnerabilities created by mutant EGFR.