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Cardamonin inhibits the expression of P-glycoprotein and enhances the anti-proliferation of paclitaxel on SKOV3-Taxol cells

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Abstract

Paclitaxel is widely used in the first-line treatment of ovarian cancer. Nevertheless, the development of acquired resistance to paclitaxel is a major obstacle for the therapy in clinic. Cardamonin is a novel anticancer chalcone which exhibits a wide range of pharmacological activities. However, the effect of cardamonin on paclitaxel-resistant ovarian cancer cells and its underlying molecular mechanisms are unknown. Here, we revealed whether cardamonin had a resensitivity for paclitaxel and furtherly explored the underlying mechanisms on SKOV3-Taxol cells. Our results showed that cardamonin combined with paclitaxel had a synergistic effect of anti-proliferation in SKOV3-Taxol cells, and CI was less than one. Cells apoptosis and G2/M phase arrest were enhanced by cardamonin with paclitaxel in a concentration-dependent way on SKOV3-Taxol cells (P < 0.05). Cardamonin significantly increased drug accumulation in SKOV3-Taxol cells (P < 0.05). Similar to verapamil, cardamonin decreased MDR1 mRNA and P-gp expression (P < 0.05). Cardamonin restrained NF-κB activation in SKOV3-Taxol cells (P < 0.05). Inhibitory effect of P-gp and NF-κB p65 (nuclear protein) expression was enhanced by cardamonin combined with PDTC, a NF-κB inhibitor. Cardamonin significantly inhibited the upregulation of NF-κB p65 (nuclear protein) and P-gp expression induced by TNF-α (P < 0.05). Taken together, cardamonin enhanced the effect of paclitaxel on inhibiting cell proliferation, inducing apoptosis and G2/M phase arrest, and then strengthened the cytotoxic effect of paclitaxel in SKOV3-Taxol cells. The mechanism might be involved in inhibition of P-gp efflux pump, reducing MDR1 mRNA and P-gp expression by cardamonin via suppression of NF-κB activation in SKOV3-Taxol cells.

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Acknowledgements

This study was supported by Natural Science Foundation of Fujian Province (Grant No. 2019J01515).

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Authors and Affiliations

  1. Department of Pharmacy, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, Fujian, China

    Qiuhua Ding, Peiguang Niu, Yanting Zhu, Huajiao Chen & Daohua Shi

  2. Fujian Key Laboratory of Women and Children’s Critical Diseases, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, Fujian, China

    Peiguang Niu & Daohua Shi

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  1. Qiuhua Ding
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  3. Yanting Zhu
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Conceived and designed the experiments: QD, DS. Performed the experiments: QD. Analyzed the data: QD, PN. Contributed reagents/materials/analysis tools: PN, YZ, HC. Wrote and revised the paper: QD, DS.

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Correspondence to Daohua Shi.

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Ding, Q., Niu, P., Zhu, Y. et al. Cardamonin inhibits the expression of P-glycoprotein and enhances the anti-proliferation of paclitaxel on SKOV3-Taxol cells. J Nat Med 76, 220–233 (2022). https://doi.org/10.1007/s11418-021-01583-1

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