Piceatannol, a Natural Analog of Resveratrol, Exerts Anti-angiogenic Efficiencies by Blockage of Vascular Endothelial Growth Factor Binding to Its Receptor
Piceatannol is also named as <i>trans</i>-3,4,3′,5′-tetrahydroxy-stilbene, which is a natural analog of resveratrol and a polyphenol existing in red wine, grape and sugar cane. Piceatannol has been proved to possess activities of immunomodulatory, anti-inflammatory, antiproliferative and...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/17/3769 |
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| author | Wei-Hui Hu Diana Kun Dai Brody Zhong-Yu Zheng Ran Duan Tina Ting-Xia Dong Qi-Wei Qin Karl Wah-Keung Tsim |
| author_facet | Wei-Hui Hu Diana Kun Dai Brody Zhong-Yu Zheng Ran Duan Tina Ting-Xia Dong Qi-Wei Qin Karl Wah-Keung Tsim |
| author_sort | Wei-Hui Hu |
| collection | DOAJ |
| description | Piceatannol is also named as <i>trans</i>-3,4,3′,5′-tetrahydroxy-stilbene, which is a natural analog of resveratrol and a polyphenol existing in red wine, grape and sugar cane. Piceatannol has been proved to possess activities of immunomodulatory, anti-inflammatory, antiproliferative and anticancer. However, the effect of piceatannol on VEGF-mediated angiogenesis is not known. Here, the inhibitory effects of piceatannol on VEGF-induced angiogenesis were tested both in vitro and in vivo models of angiogenesis. In human umbilical vein endothelial cells (HUVECs), piceatannol markedly reduced the VEGF-induced cell proliferation, migration, invasion, as well as tube formation without affecting cell viability. Furthermore, piceatannol significantly inhibited the formation of subintestinal vessel in zebrafish embryos in vivo. In addition, we identified the underlying mechanism of piceatannol in triggering the anti-angiogenic functions. Piceatannol was proposed to bind with VEGF, thus attenuating VEGF in activating VEGF receptor and blocking VEGF-mediated downstream signaling, including expressions of phosphorylated eNOS, Erk and Akt. Furthermore, piceatannol visibly suppressed ROS formation, as triggered by VEGF. Moreover, we further determined the outcome of piceatannol binding to VEGF in cancer cells: piceatannol significantly suppressed VEGF-induced colon cancer proliferation and migration. Thus, these lines of evidence supported the conclusion that piceatannol could down regulate the VEGF-mediated angiogenic functions with no cytotoxicity via decreasing the amount of VEGF binding to its receptors, thus affecting the related downstream signaling. Piceatannol may be developed into therapeutic agents or health products to reduce the high incidence of angiogenesis-related diseases. |
| first_indexed | 2024-03-10T17:12:13Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T17:12:13Z |
| publishDate | 2020-08-01 |
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| series | Molecules |
| spelling | doaj.art-90500a75916e4f66ad5c501c21606d2d2023-11-20T10:37:11ZengMDPI AGMolecules1420-30492020-08-012517376910.3390/molecules25173769Piceatannol, a Natural Analog of Resveratrol, Exerts Anti-angiogenic Efficiencies by Blockage of Vascular Endothelial Growth Factor Binding to Its ReceptorWei-Hui Hu0Diana Kun Dai1Brody Zhong-Yu Zheng2Ran Duan3Tina Ting-Xia Dong4Qi-Wei Qin5Karl Wah-Keung Tsim6Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, ChinaShenzhen Key Laboratory of Edible and Medicinal Bioresources, The Hong Kong University of Science and Technology, Hi-Tech Park, Nanshan, Shenzhen 518057, ChinaShenzhen Key Laboratory of Edible and Medicinal Bioresources, The Hong Kong University of Science and Technology, Hi-Tech Park, Nanshan, Shenzhen 518057, ChinaShenzhen Key Laboratory of Edible and Medicinal Bioresources, The Hong Kong University of Science and Technology, Hi-Tech Park, Nanshan, Shenzhen 518057, ChinaShenzhen Key Laboratory of Edible and Medicinal Bioresources, The Hong Kong University of Science and Technology, Hi-Tech Park, Nanshan, Shenzhen 518057, ChinaJoint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, ChinaShenzhen Key Laboratory of Edible and Medicinal Bioresources, The Hong Kong University of Science and Technology, Hi-Tech Park, Nanshan, Shenzhen 518057, ChinaPiceatannol is also named as <i>trans</i>-3,4,3′,5′-tetrahydroxy-stilbene, which is a natural analog of resveratrol and a polyphenol existing in red wine, grape and sugar cane. Piceatannol has been proved to possess activities of immunomodulatory, anti-inflammatory, antiproliferative and anticancer. However, the effect of piceatannol on VEGF-mediated angiogenesis is not known. Here, the inhibitory effects of piceatannol on VEGF-induced angiogenesis were tested both in vitro and in vivo models of angiogenesis. In human umbilical vein endothelial cells (HUVECs), piceatannol markedly reduced the VEGF-induced cell proliferation, migration, invasion, as well as tube formation without affecting cell viability. Furthermore, piceatannol significantly inhibited the formation of subintestinal vessel in zebrafish embryos in vivo. In addition, we identified the underlying mechanism of piceatannol in triggering the anti-angiogenic functions. Piceatannol was proposed to bind with VEGF, thus attenuating VEGF in activating VEGF receptor and blocking VEGF-mediated downstream signaling, including expressions of phosphorylated eNOS, Erk and Akt. Furthermore, piceatannol visibly suppressed ROS formation, as triggered by VEGF. Moreover, we further determined the outcome of piceatannol binding to VEGF in cancer cells: piceatannol significantly suppressed VEGF-induced colon cancer proliferation and migration. Thus, these lines of evidence supported the conclusion that piceatannol could down regulate the VEGF-mediated angiogenic functions with no cytotoxicity via decreasing the amount of VEGF binding to its receptors, thus affecting the related downstream signaling. Piceatannol may be developed into therapeutic agents or health products to reduce the high incidence of angiogenesis-related diseases.https://www.mdpi.com/1420-3049/25/17/3769piceatannolherbal medicinevasculogenesisVEGFVEGFR2pure compound |
| spellingShingle | Wei-Hui Hu Diana Kun Dai Brody Zhong-Yu Zheng Ran Duan Tina Ting-Xia Dong Qi-Wei Qin Karl Wah-Keung Tsim Piceatannol, a Natural Analog of Resveratrol, Exerts Anti-angiogenic Efficiencies by Blockage of Vascular Endothelial Growth Factor Binding to Its Receptor Molecules piceatannol herbal medicine vasculogenesis VEGF VEGFR2 pure compound |
| title | Piceatannol, a Natural Analog of Resveratrol, Exerts Anti-angiogenic Efficiencies by Blockage of Vascular Endothelial Growth Factor Binding to Its Receptor |
| title_full | Piceatannol, a Natural Analog of Resveratrol, Exerts Anti-angiogenic Efficiencies by Blockage of Vascular Endothelial Growth Factor Binding to Its Receptor |
| title_fullStr | Piceatannol, a Natural Analog of Resveratrol, Exerts Anti-angiogenic Efficiencies by Blockage of Vascular Endothelial Growth Factor Binding to Its Receptor |
| title_full_unstemmed | Piceatannol, a Natural Analog of Resveratrol, Exerts Anti-angiogenic Efficiencies by Blockage of Vascular Endothelial Growth Factor Binding to Its Receptor |
| title_short | Piceatannol, a Natural Analog of Resveratrol, Exerts Anti-angiogenic Efficiencies by Blockage of Vascular Endothelial Growth Factor Binding to Its Receptor |
| title_sort | piceatannol a natural analog of resveratrol exerts anti angiogenic efficiencies by blockage of vascular endothelial growth factor binding to its receptor |
| topic | piceatannol herbal medicine vasculogenesis VEGF VEGFR2 pure compound |
| url | https://www.mdpi.com/1420-3049/25/17/3769 |
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