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Unveiling Paclitaxel-Induced Mesenchymal Stem Cells: orchestrating Nrf2 Modulation and Apoptosis in CD44+/CD24-
Dedy Hermansyah1, Siti Syarifah2, Adi Muradi Muhar3
1Department of Surgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia.
Background:
Mesenchymal Stem Cells (MSCs) and Cancer Stem Cells (CSC) play pivotal roles in cancer progression and therapeutic responses. This study aimed to explored the effect of MSCs induced by paclitaxel on CSC expressing the CD44+/CD24- phenotype, focusing on Nrf2 modulation and apoptosis induction.
Methods:
MSCs were characterized for adherence, differentiation potential, and surface markers via standard culture, staining assays, and flow cytometry, respectively. CSCs isolated from MDA-MB-231 using MACS and were characterized based on morphology and CD44+/CD24- expression. Co-culture experiments evaluated the cytotoxic effect of Paclitaxel-induced MSCs on CSC viability using MTT assays. Flow cytometry analysis assessed apoptosis induction via annexin V-PI staining and Nrf2 and Caspase-3 gene expression were measure by qRT-PCR analysis.
Results:
MSCs exhibited typical adherence and differentiation capabilities, confirming their mesenchymal lineage. CSCs displayed an elongated morphology and expressed CD44+/CD24-, characteristic of stem-like behavior. Paclitaxel induced dose-dependent Nrf2 gene expression in MSCs. Co-culture with Paclitaxel-induced MSCs reduced CSC viability in a dose-dependent manner, with a significant decrease observed at a 5:1 MSCs:CSC ratio. Co-culture decreased the Nrf2 gene expression and increased apoptosis in CSCs, with higher caspase-3 gene expression compared to solitary paclitaxel treatment.
Conclusion:
Paclitaxel-induced MSCs decreased Nrf2 expression and significantly decreased CSC viability while enhancing apoptosis. This suggests a potential strategy to mitigate paclitaxel resistance in CD44+/CD24- CSCs. Leveraging Paclitaxel-induced MSCs presents a promising avenue for targeting Nrf2 and promoting apoptosis in CSCs, potentially improving the efficacy of chemotherapy and addressing resistance mechanisms in cancer treatment.
Insights
Paclitaxel-induced Mesenchymal Stem Cells (MSCs) reduce cancer stem cell (CSC) viability and promote apoptosis by decreasing Nrf2 expression. This approach may overcome paclitaxel resistance in CD44+/CD24- CSCs.
Area of Science:
- Cancer Biology
- Stem Cell Research
- Pharmacology
Background:
- Mesenchymal Stem Cells (MSCs) and Cancer Stem Cells (CSCs) are key players in cancer progression and treatment outcomes.
- Understanding their interaction is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the impact of paclitaxel-induced MSCs on CSCs with a CD44+/CD24- phenotype.
- To explore the modulation of Nrf2 and the induction of apoptosis in CSCs.
Main Methods:
- MSCs and CSCs (MDA-MB-231) were characterized using standard cell biology techniques and flow cytometry.
- Co-culture experiments with paclitaxel-induced MSCs assessed CSC viability (MTT assay).
- Apoptosis and gene expression (Nrf2, Caspase-3) were analyzed via flow cytometry and qRT-PCR.
Main Results:
- Paclitaxel treatment induced dose-dependent Nrf2 expression in MSCs.
- Co-culture with paclitaxel-induced MSCs significantly reduced CSC viability and Nrf2 expression.
- Enhanced apoptosis and Caspase-3 expression were observed in CSCs treated with paclitaxel-induced MSCs.
Conclusions:
- Paclitaxel-induced MSCs effectively decrease CSC viability and promote apoptosis by downregulating Nrf2.
- This strategy shows potential for overcoming paclitaxel resistance in CD44+/CD24- CSCs.
- Leveraging paclitaxel-modified MSCs offers a promising approach to improve chemotherapy efficacy and target cancer resistance mechanisms.
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