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Diosmetin induces apoptosis in ovarian cancer cells by activating reactive oxygen species and inhibiting the Nrf2 pathway

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A Correction to this article was published on 04 June 2021

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Abstract

The fatality rate of ovarian cancer ranks first among gynecological tumors, and the prognosis is poor. Diosmetin (Dio), a natural flavonoid obtained from citrus fruits, has been shown to have anti-tumor effects in lung, liver, and skin cancers. We aimed to investigate the effects of Dio on ovarian cancer A2780 and SKOV3 cells along with the underlying mechanisms. Our data showed that Dio inhibited the proliferation, migration, and invasion of these cells and induced their apoptosis. Moreover, Dio upregulated the levels of Bax and cleaved Caspase-3 and PARP while downregulating the level of Bcl2. Mechanistically, our results revealed that Dio inhibited Nrf2 and induced the production of reactive oxygen species (ROS). The ROS scavenger N-acetyl-L-cysteine (NAC) suppressed the inhibitory effect of Dio on the proliferation of the ovarian cancer cells. Additionally, overexpression of Nrf2 partially suppressed the Dio-induced apoptosis and proliferation inhibition in these cells. These findings indicate that Dio exerts an anti-tumor activity by upregulating ROS levels and inhibiting Nrf2, indicating that Dio is a promising chemotherapeutic candidate for the treatment of ovarian cancer.

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Funding

This work was supported by the National Key R&D Program of China (Grant No. 2018YFA0106902), the National Natural Science Foundation of China (Grant No. 81902637), and the Natural Science Foundation of Jilin (No. 20200404078YY).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Xinmin Road 519, Changchun, Jilin, 130001, China

    Feijie Zhao, Xiaoling Hong, Danjie Li, Zhentong Wei & Songling Zhang

  2. Institute of Translational Medicine, The First Hospital of Jilin University, Dongminzhu Road 71, Changchun, Jilin, 130001, China

    Xinxin Ci

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  1. Feijie Zhao
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  2. Xiaoling Hong
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  3. Danjie Li
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  4. Zhentong Wei
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  5. Xinxin Ci
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  6. Songling Zhang
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Contributions

Study design, Data collection, Writing the draft: FZ; Literature search: XH, DL, and ZW; Data analysis: SZ and XC.

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Correspondence to Xinxin Ci or Songling Zhang.

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Zhao, F., Hong, X., Li, D. et al. Diosmetin induces apoptosis in ovarian cancer cells by activating reactive oxygen species and inhibiting the Nrf2 pathway. Med Oncol 38, 54 (2021). https://doi.org/10.1007/s12032-021-01501-1

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