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Withaferin A inhibits proliferation of human endometrial cancer cells via transforming growth factor-β (TGF-β) signalling

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Abstract

The present study was designed to evaluate the anticancer effects of withaferin A against the human endometrial cancer via modulation of transforming growth factor-β (TGF-β) signalling. The results of the present study revealed that withaferin A exerts a dose and time-dependent antiproliferative effects against the human KLE endometrial cancer cells with comparatively lower toxicity against the THESCs normal cells. The IC50 of withaferin A against the KLE endometrial cancer cells was found to 10 μM. The results showed that withaferin A induced apoptosis and G2/M cell cycle arrest of the KLE cells which was associated with alteration of the apoptosis and cell cycle related proteins. In addition, the transwell assays showed that the migration and invasion of the KLE cells were inhibited by 53 and 40%, respectively. Finally, the effects of withaferin A were also examined on the TGF-β signalling pathway. The results showed that withaferin A blocked TGF-β-dependent Smad2 phosphorylation and expression of other TGF-β-related proteins in KLE cells. Summing up, the results suggest that withaferin A inhibits the proliferation of the human endometrial carcinoma via TGF-β signalling.

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Acknowledgements

We acknowledge the central instrumentation section of Ningbo First Hospital, Ningbo, Zhejiang, 315010, China for providing the instrumentation facility.

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Authors and Affiliations

  1. Department of obstetrics and gynaecology, Ningbo First Hospital, NO.59 of Liuting Street, Haishu District, Ningbo, 315010, Zhejiang, China

    Kejun Xu, Hongyan Shi, Yongming Du & Jilan Ou

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  1. Kejun Xu
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  2. Hongyan Shi
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  3. Yongming Du
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  4. Jilan Ou
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Contributions

Conceptualization: KX and JQ; methodology: KX, HS and YD; formal analysis and investigation: KX, HS and YD; writing—original draft preparation: YX, HS and YD; writing—review and editing critically for important intellectual content: JQ; supervision: JQ.

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Correspondence to Jilan Ou.

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All the authors declare that he has no conflict of interest.

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Xu, K., Shi, H., Du, Y. et al. Withaferin A inhibits proliferation of human endometrial cancer cells via transforming growth factor-β (TGF-β) signalling. 3 Biotech 11, 323 (2021). https://doi.org/10.1007/s13205-021-02878-6

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