Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Feb;45(2):121-127.
doi: 10.15537/smj.2024.45.2.20230478.

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

Zeliha Tuncer  1 , Ercan Kurar  1 , Tugçe Duran  1
Affiliations

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

Zeliha Tuncer et al. Saudi Med J. 2024 Feb.

Abstract

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.

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

PubMed Disclaimer

Figures

Figure 1
Figure 1
- The FACS analysis. A) The amount of MCF-7 total cell without belinostat. B) The amount of MCF-7 total cell with belinostat applied. C) Amount of CD44+/CD24- antibody treated MCF-7 stem cell without belinostat applied. D) Amount of CD44 +/CD24- antibody applied MCF-7 stem cells with belinostat applied. Q1: CD44+/CD24-, Q2: CD44+/CD24+, Q3: CD44-/CD24-, Q4: CD44-/24+
Figure 2
Figure 2
- Tumorsphere formation.
Figure 3
Figure 3
- Gene expression levels of Wnt, Hedgehog, Notch, and stem cell markers in MCF-7 cells.
Figure 4
Figure 4
- Gene expression levels of Wnt, Hedgehog, Notch, and stem cell markers in HEK-293 cells.
Figure 5
Figure 5
- Gene expression levels of Wnt, Hedgehog, Notch, and stem cell markers MCF-7 cells in MCF-7 CD44+/CD24-cancer stem cells.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin 2022; 72: 7-33. - PubMed
    1. Dick JE. Looking ahead in cancer stem cell research. Nat Biotechnol 2009; 27: 44-46. - PubMed
    1. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002; 2: 48-58. - PubMed
    1. Spillane JB, Henderson MA. Cancer stem cells: a review. ANZ J Surg 2007; 77: 464-468. - PubMed
    1. Koren E, Fuchs Y. The bad seed: cancer stem cells in tumor development and resistance. Drug Resist Updat 2016; 28: 1-12. - PubMed