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

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.

Glucosyltriazole amphiphile treatment attenuates breast cancer by modulating the AMPK signaling

“…Further, we measured the IC 50 of all the compounds (Table 2) in another TNBC cell line (4T1 cell/mouse‐derived) and results showed that compound 9h showed similar efficacy (compared with MDA‐MB‐231) in 4T1 as well (12.55 ± 0.8 µM). It was reported that cisplatin treatment in MCF‐7 and MDA‐MB‐231 cells showed IC 50 of 16.3 ± 0.53 µM and 48.1 ± 0.34 µM respectively (Koh et al, 2021; Ray et al, 2007; Vasdev et al, 2018). Compared with IC 50 of cisplatin, compound 9h showed superior activity in all three cell types.…”

Sulforaphane: An emergent anti-cancer stem cell agent

“…In addition, CSCs are intrinsically resistant to conventional therapies including chemo and radiotherapy, that mainly target high proliferative cells. CSCs are usually in a low-cycling quiescent state, which makes them almost unaffected by conventional cytotoxic agents ( 34 ).…”

Selective cytotoxicity of ent‐kaurene diterpenoids isolated from Baccharis lateralis and Baccharis retusa (Asteraceae)

“…Table 2 shows the predicted IC 50 values of compounds 1-4, calculated by the statistical tool GraphPad Prism 8, and of the positive control cisplatin [16][17][18] for human adenocarcinoma breast cancer (MDA-MB-231) and nontumorigenic (MCF-10A) cell lines.…”

“…[24] However, despite different studies describing the evaluation of the cytotoxic activity of semisynthetic derivatives of ent-kaurenoic acid, [25,26] no previous works report the selectivity against MDA-MB-231, an aggressive type of human breast adenocarcinoma cell line. .0 [16,17] MDA-MB-231 1566.0 1401.0 3072.0 1900.0 143.0 [17,18]…”