Inducing ubiquitination and degradation of TrxR1 protein by LW-216 promotes apoptosis in non-small cell lung cancer via triggering ROS production

Inducing ubiquitination and degradation of TrxR1 protein by LW-216 promotes apoptosis in non-small cell lung cancer via triggering ROS production

Blog Article

Thioredoxin reductases are frequently overexpressed in various solid tumors as a protective mechanism against heightened oxidative stress.Inhibitors of this system, such as Auranofin, are effective in eradicating cancer cells.However, the clinical significance of thioredoxin reductase 1 (TrxR1) in lung cancer, as well as the potential for its antagonist as a treatment option, necessitated further experimental validation.In this study, we observed significant upregulation of TrxR1 iphone 14 price san francisco specifically in non-small cell lung cancer (NSCLC), rather than small cell lung cancer.Moreover, TrxR1 expression exhibited associations with survival rate, tumor volume, and histological classification.

We developed a novel TrxR1 inhibitor named LW-216 and assessed its antitumor efficacy in NSCLC.Our results revealed that LW-216 is effectively bound with intracellular TrxR1 at sites R371 and G442, facilitating TrxR1 ubiquitination and suppressing TrxR1 expression, while not affecting TrxR2 expression.Treatment of LW-216-induced DNA damage and cell apoptosis in NSCLC cells through the generation of reactive oxygen species (ROS).Importantly, supplementation with N-acetylcysteine (NAC) or ectopic TrxR1 expression reversed LW-216-induced apoptosis.Furthermore, LW-216 displayed potent tumor growth inhibition in NSCLC cell-implanted mice, reducing TrxR1 expression in xenografts.

Remarkably, kicker pro comp 10 LW-216 exhibited superior antitumor activity compared to Auranofin in vivo.Collectively, our research provides compelling evidence supporting the potential of targeting TrxR1 by LW-216 as a promising therapeutic strategy for NSCLC.