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Kaempferol and Apigenin suppresses the stemness properties of TNBC cells by modulating Sirtuins

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Abstract

Sirtuins (SIRTs) overexpression serves as a potential therapeutic target for TNBC because it is associated with bioactivities of cancer stem cells (CSCs), resistance to chemotherapy, and metastasis. Irrespective of the availability of synthetic SIRT inhibitors, new SIRT inhibitors with enhanced potency and lesser side effects serve as current unmet needs. Therefore, bioactive dietary compounds; kaempferol (KMP) and apigenin (API) were investigated for their anti-SIRTs potential. We observed KMP and API inhibits cellular proliferation by DNA damage and S-phase cell cycle arrest in TNBC Cells. They also suppress stemness properties in TNBCs as observed in experiments of mammosphere formation and clonogenic potential. Our mechanistic approach indicated that KMP and API inhibited SIRT3 and SIRT6 proteins, as evidenced by our in silico and in vitro experiment. Collectively, our studies suggest that KMP and API are promising candidates to be further developed as sirtuin modulators against TNBCs.

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Acknowledgements

We acknowledge our host institute, B.V. Patel Pharmaceutical Education Research and Development (PERD) Centre, to provide us with the facilities to work. Author A. S. express gratitude to the Department of Science & Technology (DST), Ministry of Science and Technology, Government of India for INSPIRE fellowship (Grant no. IF190211).

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, Gujarat, India

    Abhilasha Sharma, Sonam Sinha, Harshita Keswani & Neeta Shrivastava

  2. Department of Life Science, Gujarat University, Ahmedabad, Gujarat, India

    Abhilasha Sharma

  3. Kashiv Biosciences, FP 27/2,43, TP-86, BLOCK-B OPP. Apple Woods Township, SP Ring Road, 382210, Ahmedabad, Gujarat, India

    Sonam Sinha

  4. Department of Biotechnology and Biochemistry, St. Xavier’s College, Ahmedabad, India

    Harshita Keswani

  5. Shri B.V. Patel Education Trust, Ahmedabad, Gujarat, India

    Neeta Shrivastava

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  1. Abhilasha Sharma
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Contributions

AS contributed to conceptualization, data curation, methodology, writing—original draft; SS contributed to conceptualization, methodology, writing—review and editing; HK contributed to methodology; NS contributed to conceptualization, supervision, writing—review and editing.

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Correspondence to Neeta Shrivastava.

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Sharma, A., Sinha, S., Keswani, H. et al. Kaempferol and Apigenin suppresses the stemness properties of TNBC cells by modulating Sirtuins. Mol Divers 26, 3225–3240 (2022). https://doi.org/10.1007/s11030-022-10384-x

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  • DOI: https://doi.org/10.1007/s11030-022-10384-x

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