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Article

Regulation of Cellular and Cancer Stem Cell-Related Putative Gene Expression of Parental and CD44+CD24 Sorted MDA-MB-231 Cells by Cisplatin

1
Faculty of Sciences and Engineering, University of Nottingham Malaysia, Semenyih 43500, Malaysia
2
China-ASEAN College of Marine Sciences, Xiamen University Malaysia, Sepang 43900, Malaysia
3
Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras 43000, Malaysia
4
Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
*
Authors to whom correspondence should be addressed.
Academic Editors: Maryam Nakhjavani, Amanda Townsend and Mary J. Meegan
Pharmaceuticals 2021, 14(5), 391; https://doi.org/10.3390/ph14050391
Received: 26 February 2021 / Revised: 4 April 2021 / Accepted: 13 April 2021 / Published: 21 April 2021
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that promotes a higher risk of metastasis and cancer reoccurrence. Cisplatin is one of the potential anticancer drugs for treating TNBC. However, the occurrence of cisplatin resistance still remains one of the challenges in fully eradicating TNBC. The presence of cancer stem cells (CSCs) has been proposed as one of the factors contributing to the development of cisplatin resistance. In this study, we aimed to characterize the cellular properties and reveal the corresponding putative target genes involved in cisplatin resistance associated with CSCs using the TNBC cell line (MDA-MB-231). CSC-like cells were isolated from parental cells and the therapeutic effect of cisplatin on CSC-like cells was compared to that of the parental cells via cell characterization bioassays. A PCR array was then conducted to study the expression of cellular mRNA for each subpopulation. As compared to treated parental cells, treated CSCs displayed lower events of late apoptosis/necrosis and G2/M phase cell arrest, with higher mammosphere formation capacity. Furthermore, a distinct set of putative target genes correlated to the Hedgehog pathway and angiogenesis were dysregulated solely in CSC-like cells after cisplatin treatment, which were closely related to the regulation of chemoresistance and self-renewability in breast cancer. In summary, both cellular and gene expression studies suggest the attenuated cytotoxicity of cisplatin in CSC-like cells as compared to parental cells. Understanding the role of dysregulated putative target genes induced by cisplatin in CSCs may aid in the potential development of therapeutic targets for cisplatin-resistant breast cancer. View Full-Text
Keywords: triple-negative breast cancer; cisplatin resistance; cancer stem cells; Hedgehog pathway; angiogenesis triple-negative breast cancer; cisplatin resistance; cancer stem cells; Hedgehog pathway; angiogenesis
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MDPI and ACS Style

Koh, M.Z.; Ho, W.Y.; Yeap, S.K.; Ali, N.M.; Boo, L.; Alitheen, N.B. Regulation of Cellular and Cancer Stem Cell-Related Putative Gene Expression of Parental and CD44+CD24 Sorted MDA-MB-231 Cells by Cisplatin. Pharmaceuticals 2021, 14, 391. https://doi.org/10.3390/ph14050391

AMA Style

Koh MZ, Ho WY, Yeap SK, Ali NM, Boo L, Alitheen NB. Regulation of Cellular and Cancer Stem Cell-Related Putative Gene Expression of Parental and CD44+CD24 Sorted MDA-MB-231 Cells by Cisplatin. Pharmaceuticals. 2021; 14(5):391. https://doi.org/10.3390/ph14050391

Chicago/Turabian Style

Koh, May Z., Wan Y. Ho, Swee K. Yeap, Norlaily M. Ali, Lily Boo, and Noorjahan B. Alitheen. 2021. "Regulation of Cellular and Cancer Stem Cell-Related Putative Gene Expression of Parental and CD44+CD24 Sorted MDA-MB-231 Cells by Cisplatin" Pharmaceuticals 14, no. 5: 391. https://doi.org/10.3390/ph14050391

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