RETRACTED ARTICLE: Belinostat suppresses cell proliferation by inactivating Wnt/β-catenin pathway and promotes apoptosis through regulating PKC pathway in breast cancer

Abstract

Belinostat is a histone deacetylase inhibitor drug capable of regulating cell growth in diverse cancers. Nonetheless, little information clarified the role of Belinostat in breast cancer. Hence, the functions of Belinostat in breast cancer cells survival was disclosed in this study. Belinostat at 50 and 100 lM were applied to manage MCF-7 cells, cell viability, Ki67 positive cells, cell cycle and apoptosis were monitored via MTT, immunohistochemistry and flow cytometry. Furthermore, the apoptosis-related factors, Wnt/b-catenin pathway and PKC pathway were tested through western blot and qRT-PCR. Lastly, in vivo effect of Belinostat was determined by a murine model. The results showed that Belinostat dampened cell viability, decreased the proportion of Ki67 positive cells and arrested cells at G0/G1 phase. The decreases of Wnt/b-catenin, CCND2 and Myc were observed in MCF-7 cells after Belinostat stimulation. Additionally, Belinostat induced cell apoptosis, meanwhile dampened Bcl-2 and raised Bax and Cleaved caspase 3 in a dose and time-dependent manner. Additionally, Belinostat activated PKC pathway by upgrading PKCd and P53 expressions. Furthermore, Belinostat restrained tumour weight and volume in vivo. In summary, this study depicted that Belinostat prohibited proliferation and evoked apoptosis via mediating Wnt/b-catenin and PKC pathways in MCF-7 cells.

The Role of Notch, Hedgehog, and Wnt Signaling Pathways in the Resistance of Tumors to Anticancer Therapies

“…Several inhibitors that target apoptosis regulation by modulating Wnt signaling have been investigated. For example, Belinostat is a histone deacetylase inhibitor that induces apoptosis by decreasing the Wnt/β-catenin, CCND2, and Myc in MCF-7 cells (Lu et al, 2019). Lanatoside C inhibits Wnt/β-catenin signaling by down-regulating c-Myc in gastric cancer cells, while overexpression of c-Myc reverses the antitumor effect of lanatoside C, suggesting that c-Myc is a key drug target of lanatoside C (Hu et al, 2018).…”

Anti-tumor activity of resveratrol against gastric cancer: a review of recent advances with an emphasis on molecular pathways

“…Chemotherapeutic activity of Res mainly depends on its impact on PKC. A growing body of evidence demonstrates that PKC participates in tumor progression, tumor proliferation, tumor viability and tumor migration [ 106 – 108 ]. Res exerts a negligible impact on cell lysis, while it considerably induces G 0 /G 1 cell cycle arrest and apoptosis by down-regulation of PKC [ 109 ] demonstrating the potential role of this signaling pathway in progression and malignancy of GC cells.…”

Targeting Histone Modifications in Breast Cancer: A Precise Weapon on the Way

“…Paradoxically, SAHA also promotes the EMT and metastasis of TNBC cells by inhibiting HDAC8, which highlights the importance of caution when using SAHA to treat BC, given its potential to promote metastasis ( Wu et al, 2016 ). Belinostat (PXD101) also inhibits proliferation and induces apoptosis via the Wnt/β-catenin and PKC pathways, with synergistic effects observed for a combination of belinostat and a HSP90 inhibitor (17-AAG) ( Lu et al, 2019 ; Zuo et al, 2020 ). Panobinostat (LBH-589) can reverse the EMT in TNBC by inhibiting ZEB1/2 ( Rhodes et al, 2014 ).…”