Arsenic trioxide inhibits viability and induces apoptosis through reactivating the Wnt inhibitor secreted frizzled related protein-1 in prostate cancer cells

Abstract

BackgroundGrowing evidence suggests that arsenic trioxide (As2O3) induces apoptosis and inhibits tumor cell growth in prostate cancer (PCa), although details of the mechanism are still inconclusive. We investigated the antitumor effect of As2O3 in human PCa cell lines LNCaP and PC3 and the underlying mechanisms by focusing on the Wnt signaling pathway.MethodsThe effect of As2O3 on the viability and apoptosis of PCa cells was investigated by cholecystokinin-8 and flow cytometry. The expression of the related proteins in the Wnt signaling pathway and the downstream target genes of the Wnt signaling pathway was examined by Western blot and quantitative real-time PCR assay. The methylation status of the SFRP1 gene promoter was assessed by bisulfite sequencing.ResultsAs2O3 inhibited the viability of PCa cells and induced apoptosis of PCa cells in a dose-dependent manner. The protein level of phosphoglycogen synthase kinase-3β was upregulated, whereas the protein level of β-catenin and the mRNA levels of c-MYC, MMP-7, and COX-2 were downregulated in a dose-dependent manner in PCa cells treated with As2O3. In addition, As2O3 upregulated the protein and mRNA levels of secreted frizzled related protein-1, and increased the demethylation of the SFRP1 gene promoter.ConclusionOur results suggest that As2O3 may inhibit cell viability and induce apoptosis through reactivating the Wnt inhibitor secreted frizzled related protein-1 in both androgen-dependent and -independent human PCa.

Arsenic Trioxide Induces Retinoic Acid-Related Orphan Receptor Beta and Blocks the WNT Pathway to Inhibit Stemness in Glioblastoma

“…The WNT/β-Catenin pathway is considered a key mediator of biological functions including cell proliferation, metabolism, angiogenesis, and EMT, and targeting this pathway can disrupt critical functions of brain tumor cells to attain critical progress in alternative GBM therapeutic strategies, thus enhancing the survival of GBM patients (Barzegar Behrooz et al 2022). Of note, ATO is revealed to potentiate tumor cell apoptosis and suppress viability in part via downregulation of the WNT/β-Catenin pathway in mantle cell lymphoma (Li et al 2017) and prostate cancer (Zheng et al 2016). In this study, the activity of the WNT/β-Catenin pathway in GBM cells was decreased by ATO treatment.…”

Arsenic Trioxide Suppressed Migration and Angiogenesis by Targeting FOXO3a in Gastric Cancer Cells

“…A low dosage of As 2 O 3 inhibited angiogenesis in epithelial ovarian cancer without cell viability or apoptosis [6]. As 2 O 3 inhibited cell viability and induced apoptosis by reactivating the Wnt inhibitor secreted frizzled-related protein-1 in human prostate cancer cells [7]. In the present study, we tried to investigate the effect of As 2 O 3 on the migration and angiogenesis of gastric cancer cells and its underlying molecular mechanism.…”