Regulation of Cellular and Cancer Stem Cell-Related Putative Gene Expression of Parental and CD44CD24 Sorted MDA-MB-231 Cells by Cisplatin

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2021 Apr 30

PMID 33919109

Citations 5

Authors

May Zie Koh

Wan Yong Ho

Swee Keong Yeap

Norlaily Mohd Ali

Lily Boo

Noorjahan Banu Alitheen

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Cytotoxic and proliferation-inhibitory activity of natural and synthetic fungal tropolone sesquiterpenoids in various cell lines.

Bergmann T, Menssen M, Schotte C, Cox R, Lee-Thedieck C Heliyon. 2025; 10(22):e37713.

PMID: 39748960 PMC: 11693898. DOI: 10.1016/j.heliyon.2024.e37713.

Green Tea Leaves and Rosemary Extracts Selectively Induce Cell Death in Triple-Negative Breast Cancer Cells and Cancer Stem Cells and Enhance the Efficacy of Common Chemotherapeutics.

Raad C, Raad A, Pandey S Evid Based Complement Alternat Med. 2024; 2024:9458716.

PMID: 39376573 PMC: 11458307. DOI: 10.1155/2024/9458716.

Cancer stem cells: advances in knowledge and implications for cancer therapy.

Chu X, Tian W, Ning J, Xiao G, Zhou Y, Wang Z Signal Transduct Target Ther. 2024; 9(1):170.

PMID: 38965243 PMC: 11224386. DOI: 10.1038/s41392-024-01851-y.

Sulforaphane: An emergent anti-cancer stem cell agent.

Coutinho L, Tortelli Junior T, Rangel M Front Oncol. 2023; 13:1089115.

PMID: 36776295 PMC: 9909961. DOI: 10.3389/fonc.2023.1089115.

Cytotoxicity towards Breast Cancer Cells of Pluronic F-127/Hyaluronic Acid Hydrogel Containing Nitric Oxide Donor and Silica Nanoparticles Loaded with Cisplatin.

Santana B, Pieretti J, Gomes R, Cerchiaro G, Seabra A Pharmaceutics. 2022; 14(12).

PMID: 36559330 PMC: 9780945. DOI: 10.3390/pharmaceutics14122837.

References

Abdullah L, Chow E . Mechanisms of chemoresistance in cancer stem cells. Clin Transl Med. 2013; 2(1):3. PMC: 3565873. DOI: 10.1186/2001-1326-2-3. View

Deng X, Apple S, Zhao H, Song J, Lee M, Luo W . CD24 Expression and differential resistance to chemotherapy in triple-negative breast cancer. Oncotarget. 2017; 8(24):38294-38308. PMC: 5503533. DOI: 10.18632/oncotarget.16203. View

Jansson S, Aaltonen K, Bendahl P, Falck A, Karlsson M, Pietras K . The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence. Breast Cancer Res Treat. 2018; 169(2):231-241. PMC: 5945746. DOI: 10.1007/s10549-018-4664-7. View

Sladek N, Kollander R, Sreerama L, Kiang D . Cellular levels of aldehyde dehydrogenases (ALDH1A1 and ALDH3A1) as predictors of therapeutic responses to cyclophosphamide-based chemotherapy of breast cancer: a retrospective study. Rational individualization of oxazaphosphorine-based cancer.... Cancer Chemother Pharmacol. 2002; 49(4):309-21. DOI: 10.1007/s00280-001-0412-4. View

Kida K, Ishikawa T, Yamada A, Shimada K, Narui K, Sugae S . Effect of ALDH1 on prognosis and chemoresistance by breast cancer subtype. Breast Cancer Res Treat. 2016; 156(2):261-9. DOI: 10.1007/s10549-016-3738-7. View

Abraham B, Fritz P, McClellan M, Hauptvogel P, Athelogou M, Brauch H . Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res. 2005; 11(3):1154-9. View

Cancello G, Bagnardi V, Sangalli C, Montagna E, Dellapasqua S, Sporchia A . Phase II Study With Epirubicin, Cisplatin, and Infusional Fluorouracil Followed by Weekly Paclitaxel With Metronomic Cyclophosphamide as a Preoperative Treatment of Triple-Negative Breast Cancer. Clin Breast Cancer. 2015; 15(4):259-65. DOI: 10.1016/j.clbc.2015.03.002. View

Zeng Q, Li S, Chepeha D, Giordano T, Li J, Zhang H . Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signaling. Cancer Cell. 2005; 8(1):13-23. DOI: 10.1016/j.ccr.2005.06.004. View

Zhong Y, Shen S, Zhou Y, Mao F, Lin Y, Guan J . NOTCH1 is a poor prognostic factor for breast cancer and is associated with breast cancer stem cells. Onco Targets Ther. 2016; 9:6865-6871. PMC: 5106235. DOI: 10.2147/OTT.S109606. View

10.

Petrelli F, Barni S, Bregni G, De Braud F, Di Cosimo S . Platinum salts in advanced breast cancer: a systematic review and meta-analysis of randomized clinical trials. Breast Cancer Res Treat. 2016; 160(3):425-437. DOI: 10.1007/s10549-016-4025-3. View

11.

Peitsch M, Muller C, Tschopp J . DNA fragmentation during apoptosis is caused by frequent single-strand cuts. Nucleic Acids Res. 1993; 21(18):4206-9. PMC: 310051. DOI: 10.1093/nar/21.18.4206. View

12.

Somali I, Alacacioglu A, Tarhan M, Meydan N, Erten C, Usalp S . Cisplatin plus gemcitabine chemotherapy in taxane/anthracycline-resistant metastatic breast cancer. Chemotherapy. 2009; 55(3):155-60. DOI: 10.1159/000214143. View

13.

Carter B, Qiu Y, Huang X, Diao L, Zhang N, Coombes K . Survivin is highly expressed in CD34(+)38(-) leukemic stem/progenitor cells and predicts poor clinical outcomes in AML. Blood. 2012; 120(1):173-80. PMC: 3390955. DOI: 10.1182/blood-2012-02-409888. View

14.

Basu A, Krishnamurthy S . Cellular responses to Cisplatin-induced DNA damage. J Nucleic Acids. 2010; 2010. PMC: 2929606. DOI: 10.4061/2010/201367. View

15.

Hu X, Zhang J, Xu B, Cai L, Ragaz J, Wang Z . Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2015; 16(4):436-46. DOI: 10.1016/S1470-2045(15)70064-1. View

16.

Seyfried T, Huysentruyt L . On the origin of cancer metastasis. Crit Rev Oncog. 2012; 18(1-2):43-73. PMC: 3597235. DOI: 10.1615/critrevoncog.v18.i1-2.40. View

17.

Yang Z, Guo F, Albers A, Sehouli J, Kaufmann A . Disulfiram modulates ROS accumulation and overcomes synergistically cisplatin resistance in breast cancer cell lines. Biomed Pharmacother. 2019; 113:108727. DOI: 10.1016/j.biopha.2019.108727. View

18.

Casciano J, Perry C, Cohen-Nowak A, Miller K, Vande Voorde J, Zhang Q . MYC regulates fatty acid metabolism through a multigenic program in claudin-low triple negative breast cancer. Br J Cancer. 2020; 122(6):868-884. PMC: 7078291. DOI: 10.1038/s41416-019-0711-3. View

19.

ONeill C, Urs S, Cinelli C, Lincoln A, Nadeau R, Leon R . Notch2 signaling induces apoptosis and inhibits human MDA-MB-231 xenograft growth. Am J Pathol. 2007; 171(3):1023-36. PMC: 1959488. DOI: 10.2353/ajpath.2007.061029. View

20.

Yu W, Wang Z, Fong C, Liu D, Yip T, Au S . Chemoresistant lung cancer stem cells display high DNA repair capability to remove cisplatin-induced DNA damage. Br J Pharmacol. 2016; 174(4):302-313. PMC: 5289946. DOI: 10.1111/bph.13690. View