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Morin inhibits colon cancer stem cells by inhibiting PUM1 expression in vitro

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Abstract

Over the last few decades, the number of people diagnosed with cancer has increased dramatically every year, making it a major cause of mortality today. Colon cancer is the third most common cancer worldwide, and the second in mortality rate. Current cancer treatment fails to treat colon cancer completely due to the remains of Cancer Stem Cells (CSCs). Morin flavonoid present in figs (Ficus carica) and other plant sources, was found to have an anti-proliferative effect on the colon cancer model and cell line, but it is not studied for its effect on the colon CSCs. In this study, we have tested the potency of morin to inhibit CSCs. We found that morin has significantly reduced colon cancer cell proliferation, colony formation, migration, and colonospheroid formation in a dose-dependent manner. Pumilio-1 (PUM1) has been shown to play an important role in colon CSCs maintenance. We found that morin has a good binding affinity with PUM1 protein with one hydrophobic and two hydrogen bond interactions. Further, the immunofluorescence results have also shown a reduction in PUM1 expression in colon cancer cell lines after morin treatment. CD133 is overexpressed in colon CSCs and morin treatment has reduced the CD133 expression in HCT116 and CT26 colon cancer cell lines. Our research outcome has explored the anti-cancer stem cell potency of morin via targeting the PUM1 protein and further reducing the colon spheroids formation and reducing the CD133 expression in colon cancer cells.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

All persons who have made substantial contributions to the work reported in the manuscript (e.g., technical help, writing and editing assistance, general support, but who do not meet the criteria for authorship, are named in the Acknowledgements and have given us their written permission to be named. If we have not included an Acknowledgements, then that indicates that we have not received substantial contributions from non-authors

Funding

The authors would like to express their gratitude to the SRM Institute of Science and Technology in Kattankulathur for funding this research and providing the laboratory facility. We would like to thank the Science and Engineering Research Board (SERB)-(EMR/2017/002874) and the Department of Biotechnology, India-(DBTBT/PR26189/GET/119/226/2017) for funding and support to carry out this research.

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Authors and Affiliations

  1. Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, 603203, India

    Ravi Gor & Satish Ramalingam

  2. Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, 603203, India

    Linkon Saha, Sparsh Agarwal, Urekha Karri, Advait Sohani & Raman Pachaiappan

  3. Department of Genetic Engineering, Computational Biology Laboratory, SRM Institute of Science and Technology, Kattankulathur, 603203, India

    Thirumurthy Madhavan

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All persons who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take public responsibility for the content, including participation in the concept, design, analysis, writing, or revision of the manuscript. Furthermore, each author certifies that this material or similar material has not been and will not be submitted to or published in any other publication before its appearance in Medical Oncology. Conception and design of the Study: SR, RG. Acquisition of data: RG, LS, UK, SA, AS. Analysis and/or interpretation of data: RG, LS, UK, SA, AS, SR. Drafting the manuscript: RG, LS, UK, SA, AS. Revising the manuscript critically for important intellectual content: RG, LS, UK, SA, AS, TM, RP, SR. Approval of the version of the manuscript to be published RG, LS,, UK, SA, A, TM, RP, SR.

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Correspondence to Satish Ramalingam.

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Gor, R., Saha, L., Agarwal, S. et al. Morin inhibits colon cancer stem cells by inhibiting PUM1 expression in vitro. Med Oncol 39, 251 (2022). https://doi.org/10.1007/s12032-022-01851-4

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