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Curcumin sensitizes carboplatin treatment in triple negative breast cancer through reactive oxygen species induced DNA repair pathway

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Abstract

Background

As patients with triple-negative breast cancer (TNBC) have a very weak response to hormone inhibition or anti-HER2 therapy, traditional chemotherapy is commonly used in these patients. Recently, carboplatin has been approved for the clinical treatment of TNBC. However, several patients exhibit resistance to carboplatin treatment. Therefore, strategies to enhance the antitumor effect of carboplatin need to be explored. In our study, we investigated the function of curcumin in increasing the response to carboplatin.

Methods and results

MTT and colony formation assays were used to evaluate cell viability after carboplatin and curcumin treatment. In addition, we conducted flow cytometric and Western blot analyses to examine cellular apoptosis. Subsequently, molecular and biochemical experiments were used to explore the mechanism by which curcumin sensitized TNBC to carboplatin treatment. We demonstrated that different TNBC cells responded differently to carboplatin. Low-dose carboplatin killed CAL-51 cells but barely influenced CAL-51-R and MDA-MB-231 cells. To improve the sensitivity of resistant TNBC cells to carboplatin, combined treatment with curcumin was applied and was found to inhibit proliferation and induce apoptosis. Mechanistically, curcumin exerted its anticancer effect by increasing reactive oxygen species (ROS) production, which downregulated the DNA repair protein RAD51, leading to upregulation of γH2AX. As expected, ROS scavenger NAC reversed the inhibitory effect on growth and DNA repair pathway activity mediated by curcumin.

Conclusion

Collectively, our data demonstrate that curcumin sensitizes TNBC to the anticancer effect of carboplatin by increasing ROS-induced DNA damage, thus providing an effective combination treatment strategy for TNBC.

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Data availability

The data used to support this study are included within the article.

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Acknowledgements

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Funding

This work was supported by the research grants from the National Natural Science Foundation of China (Grants Number: 81901567), the Natural Science Foundation of Hubei Province (Grants Number: 2018CFB112), the Natural Science Foundation of Hubei Provincial Department of Education (Q20202105), the Cultivating Project for Young Scholar at Hubei University of Medicine (Grants Number: 2017QDJZR07), the Scientific and Technological Project of Shiyan City of Hubei Province (Grants Number: 19Y03).

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Authors and Affiliations

  1. Department of General Surgery, Section IV, Xiangyang No.1 People’s Hospital, Hubei University of Medicine, No.15 Jiefang Road, Fancheng District, Xiangyang, 441000, Hubei, China

    Genjin Wang, Zhengkuo Wei & Feng Liu

  2. Department of Obstetrics and Gynaecology, Xiangyang No.1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, China

    Peng Duan

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  1. Genjin Wang
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  4. Feng Liu
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Contributions

GW and PD conceived and designed the experiments. GW, ZW and FL performed the experiments. GW, PD and ZW analyzed the data. GW and PD contributed reagents and materials. GW, PD and ZW wrote the manuscript. All the authors have approved the final version of this manuscript.

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Correspondence to Genjin Wang.

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Wang, G., Duan, P., Wei, Z. et al. Curcumin sensitizes carboplatin treatment in triple negative breast cancer through reactive oxygen species induced DNA repair pathway. Mol Biol Rep 49, 3259–3270 (2022). https://doi.org/10.1007/s11033-022-07162-1

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  • DOI: https://doi.org/10.1007/s11033-022-07162-1

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