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Flavone inhibits migration through DLC1/RhoA pathway by decreasing ROS generation in breast cancer cells

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Abstract

Tumor suppressor protein deleted in liver cancer 1 (DLC1) is a RhoGTPase-activating protein (RhoGAP) and inhibits cancer cell migration by inactivating downstream target protein RhoA. A few studies have reported the regulations of reactive oxygen species (ROS) on RhoGAP. In this study, we investigated flavone (the core structure of flavonoids)-induced regulation on ROS generation and DLC1/RhoA pathway in MCF-7 and MDA-MB-231 breast cancer cells and explored whether flavone-induced upregulation of DLC1 is mediated by ROS. Our results showed that flavone decreased ROS production and inhibited cell migration through DLC1/RhoA pathway. To further investigate the role of ROS in flavone-induced regulation on DLC1/RhoA pathway, hydrogen peroxide was added to restore the ROS levels. Flavone-induced upregulation of DLC1 expression, downregulation of RhoA activity, and inhibition of cell migration were all restrained by hydrogen peroxide. We also found that flavone increased DLC1 stability by inhibiting DLC1 protein degradation in breast cancer cells. In summary, our study demonstrated that flavone inhibited cell migration through DLC1/RhoA pathway by decreasing ROS generation and suppressed DLC1 degradation in MCF-7 and MDA-MB-231 breast cancer cells.

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Acknowledgments

This work was supported by the special funds of the National Natural Science Foundation of China (Grant No. 31340035), the Major Key Science and Technology Project of Shandong Province (2015ZDJS04003), the Science and Technology Development Program of Shandong Province (2012CSF12112), the Key Program of Shandong Provincial Natural Science Foundation (ZR2013CZ002), the Research Fund for the Doctoral Program of Higher Education of China (20113704110004), and the Science and Technology Program of Jinan (201202033).

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Authors and Affiliations

  1. Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China

    Wenzhen Zhu, Long Ma, Bingwu Yang, Zhaodi Zheng, Rongfei Chai, Tingting Liu, Zhaojun Liu, Taiyu Song, Fenglin Li & Guorong Li

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  1. Wenzhen Zhu
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  2. Long Ma
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  3. Bingwu Yang
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  9. Fenglin Li
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  10. Guorong Li
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Correspondence to Guorong Li.

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Editor: Tetsuji Okamoto

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Zhu, W., Ma, L., Yang, B. et al. Flavone inhibits migration through DLC1/RhoA pathway by decreasing ROS generation in breast cancer cells. In Vitro Cell.Dev.Biol.-Animal 52, 589–597 (2016). https://doi.org/10.1007/s11626-016-0010-8

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