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Flavone inhibits migration through DLC1/RhoA pathway by decreasing ROS generation in breast cancer cells
Wenzhen Zhu1, Long Ma1, Bingwu Yang1
1Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China.
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.
Insights
Flavone inhibits breast cancer cell migration by regulating the DLC1/RhoA pathway and decreasing reactive oxygen species (ROS). This compound also enhances DLC1 protein stability, offering a potential therapeutic strategy.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Tumor suppressor protein deleted in liver cancer 1 (DLC1) is a RhoGAP that inhibits cancer cell migration.
- Reactive oxygen species (ROS) are known to regulate RhoGAP activity.
Purpose of the Study:
- To investigate flavone's effect on ROS generation and the DLC1/RhoA pathway in breast cancer cells.
- To determine if ROS mediates flavone-induced DLC1 upregulation.
Main Methods:
- Utilized MCF-7 and MDA-MB-231 breast cancer cell lines.
- Assessed ROS levels, DLC1 expression, RhoA activity, and cell migration.
- Investigated the role of ROS by restoring levels with hydrogen peroxide.
- Examined DLC1 protein stability and degradation.
Main Results:
- Flavone decreased ROS production and inhibited cell migration via the DLC1/RhoA pathway.
- Restoring ROS levels with hydrogen peroxide counteracted flavone's effects on DLC1, RhoA, and cell migration.
- Flavone enhanced DLC1 stability by reducing its protein degradation.
Conclusions:
- Flavone inhibits breast cancer cell migration by decreasing ROS and modulating the DLC1/RhoA pathway.
- Flavone's mechanism involves enhancing DLC1 stability and reducing protein degradation.
- These findings highlight flavone as a potential therapeutic agent targeting cancer cell migration.
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