Investigation of the effect of belinostat on MCF-7 breast cancer stem cells via the Wnt, Notch, and Hedgehog signaling pathway

Objectives: To evaluate belinostat's (PXD101) activity on MCF-7 breast Cancer Stem Cells (CSCs) via Wnt, Notch, and Hedgehog.

Methods: This research study was carried out at the Department of Medical Biology, Necmettin Erbakan University, Konya, Turkey, from June 2017 to July 2019. The effect of PXD101 on MCF-7 cell viability was determined by cell proliferation kit (XTT). Following belinostat treatment, CD44+/CD24- MCF-7 CSCs were isolated by FACS. Ribonucleic acid isolation and copy-deoxyribonucleic acid synthesis were carried out using HEK-293 cells, MCF-7 cells, and MCF-7 CSCs. Expression changes of metastasis-related genes, Wnt, Hedgehog, Notch, and stem cell markers were analysed by quantitative polymerase chain reaction. The IC50 in MCF-7 Cancer cells was 5 μM for 48 hours. The FACS analysis indicated that 2% of the MCF-7 Cancer cells were CSCs. Following belinostat treatment, the MCF-7 cell count decreased by 44%, and the MCF-7 CD44+/CD24- CSC count decreased by 66%.

Results: Belinostat treatment reduced the expression of metastasis, Wnt, Notch, Hedgehog, and stem cell marker genes.

Conclusion: Belinostat has a potential effect on the differentiation and self-renewal of breast CSCs.

Hedgehog; MCF-7; Wnt; belinostat; cancer stem cell.