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Cell cycle arrest-mediated cell death by morin in MDA-MB-231 triple-negative breast cancer cells
Sushma Maharjan1, Yun-Suk Kwon1, Min-Gu Lee1
1Department of Pharmacology, College of Medicine and Intractable Disease Research Center, Dongguk University, Gyeongju, 38066, Republic of Korea.
Background:
Morin, a flavonoid extracted from Moraceace family and exhibits several pharmacological activities including anti-cancer activity. Although the anticancer activity of morin in breast cancer was estimated in some investigations, the pharmaceutical mechanism has not been fully elucidated. Therefore, we investigated to unveil the detail signaling pathway in morin-treated in MDA-MB-231 triple-negative breast cancer cells.
Methods:
The cytotoxicity of morin in MDA-MB-231 cells was confirmed by sulforhodamine B (SRB) assay and colony formation assay. Flow cytometry was performed to examine the cell cycle and cell death patterns and the protein expression and phosphorylation were detected by western blotting.
Results:
Our results showed that morin inhibited MDA-MB-231 cells proliferation in time and concentration-dependent manner. Morphological changes were observed when treated with various concentration of morin in MDA-MB-231 cells. In regard to protein expression, morin induced the phosphorylation of ERK and p-H2A.X and decreased the level of DNA repair markers, RAD51 and survivin. In addition, flow cytometry showed S and G2/M arrest by morin that was associated with the decrease in the protein expression of cyclin A2 and cyclin B1 and upregulation of p21. Interestingly, annexin V/PI staining result clearly showed that morin induced cell death without apoptosis. Furthermore, attenuated FoxM1 by morin was co-related with cell cycle regulators including p21, cyclin A2 and cyclin B1.
Conclusion:
Taken together, our study indicates that morin-induced cell death of MDA-MB-231 is caused by sustained cell cycle arrest via the induction of p21 expression by activation of ERK and repression of FOXM1 signaling pathways.
Insights
Morin, a flavonoid, effectively inhibits triple-negative breast cancer cell proliferation by inducing sustained cell cycle arrest. This occurs through ERK activation and FOXM1 repression, leading to cell death without apoptosis.
Area of Science:
- Pharmacology
- Molecular Biology
- Cancer Research
Background:
- Morin, a flavonoid from the Moraceace family, possesses known pharmacological activities, including anti-cancer properties.
- While morin's anti-cancer effects on breast cancer have been studied, its precise pharmaceutical mechanisms remain incompletely understood.
- This study focuses on elucidating the detailed signaling pathways involved in morin's action on MDA-MB-231 triple-negative breast cancer cells.
Purpose of the Study:
- To investigate the detailed signaling pathway of morin in MDA-MB-231 triple-negative breast cancer cells.
- To understand the mechanism of morin-induced anti-cancer effects.
- To explore morin's impact on cell proliferation, cell cycle, and cell death.
Main Methods:
- Cytotoxicity was assessed using sulforhodamine B (SRB) and colony formation assays.
- Flow cytometry was employed to analyze cell cycle progression and cell death patterns.
- Western blotting was used to detect protein expression and phosphorylation levels.
Main Results:
- Morin demonstrated dose- and time-dependent inhibition of MDA-MB-231 cell proliferation, inducing morphological changes.
- Morin triggered ERK and p-H2A.X phosphorylation while decreasing RAD51 and survivin levels.
- Cell cycle analysis revealed S and G2/M phase arrest, linked to reduced cyclin A2/B1 and increased p21 expression. Morin induced non-apoptotic cell death and attenuated FoxM1, correlating with cell cycle regulators.
Conclusions:
- Morin induces cell death in MDA-MB-231 cells through sustained cell cycle arrest.
- This arrest is mediated by p21 induction via ERK activation.
- The mechanism also involves the repression of FOXM1 signaling pathways.
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