Zhou 2018 Free Radic Biol Med

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Zhou L, Yi Y, Yuan Q, Zhang J, Li Y, Wang P, Xu M, Xie S (2018) VAOS, a novel vanadyl complexes of alginate saccharides, inducing apoptosis via activation of AKT-dependent ROS production in NSCLC. Free Radic Biol Med 129:177-85.

» PMID: 30223019

Zhou L, Yi Y, Yuan Q, Zhang J*, Li Y*, Wang P, Xu M, Xie S (2018) Free Radic Biol Med

Abstract: Previous studies have confirmed that protein tyrosine phosphatase 1B (PTP1B) can promote tumour progression in non-small cell lung cancer (NSCLC). Vanadyl alginate oligosaccharides (VAOS) is a new coordination compounds that possesses a good PTP1B inhibitory activity. However, the potent anticancer efficacy of VAOS in human NSCLC requires further study. In this study, VAOS exhibited effective inhibitory effects in NSCLC both in cultured cells and in a xenograft mouse model. VAOS was further identified to induce NSCLC cell apoptosis through activating protein kinase B (AKT) to elevate intracellular reactive oxygen species (ROS) levels by increasing in oxygen consumption and impairing the ROS-scavenging system. Neither silencing of PTP1B by siRNA nor transient overexpression of PTP1B had an effect on the AKT phosphorylation triggered by VAOS, indicating that PTP1B inhibition was not involved in VAOS-induced apoptosis. Through phosphorus colorimetric assay, we demonstrated that VAOS notably inhibited phosphatase and tensin homologue deleted on chromosome 10 (PTEN) dephosphorylation activity, another member of the protein tyrosine phosphatases (PTPases)-upstream factor of AKT. Interestingly, PTEN knockdown sensitized cells to VAOS, whereas ectopic expression of PTEN markedly rescued VAOS-mediated lethality. In vivo, VAOS treatment markedly reduced PTEN activity and tumour cell burden with low systemic toxicity. Thus, our data not only provided a new therapeutic drug candidate for NSCLC, but presented new understanding into the pharmacological research of VAOS.

Keywords: AKT, Non-small cell lung cancer, PTEN, ROS, Vanadyl alginate oligosaccharides, A549 adenocarcinomic human alveolar basal epithelial cells Bioblast editor: Plangger M

Labels: MiParea: Respiration, nDNA;cell genetics, Genetic knockout;overexpression, Pharmacology;toxicology  Pathology: Cancer  Stress:Cell death  Organism: Human  Tissue;cell: Lung;gill  Preparation: Intact cells 

Coupling state: ROUTINE 

HRR: Oxygraph-2k