Inhibitory Effects of Euphorbia ebracteolata Hayata Extract ECB on Melanoma-Induced Hyperplasia of Blood Vessels in Zebrafish Embryos

Wenjing Dong; Xinyue Han; Chao Bao; Saijilahu Tai; Yuxia Bai; Liang Xu; Jingfeng Yang; TinChung Leung; Wuliji Ao; Wu Dong

doi:10.1155/2021/5543259

Inhibitory Effects of Euphorbia ebracteolata Hayata Extract ECB on Melanoma-Induced Hyperplasia of Blood Vessels in Zebrafish Embryos

Evid Based Complement Alternat Med. 2021 Apr 26:2021:5543259. doi: 10.1155/2021/5543259. eCollection 2021.

Authors

Wenjing Dong¹, Xinyue Han¹, Chao Bao¹, Saijilahu Tai², Yuxia Bai³, Liang Xu⁴, Jingfeng Yang¹, TinChung Leung⁵, Wuliji Ao³, Wu Dong¹

Affiliations

¹ Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicant and Toxicology, College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia 028000, China.
² Mongolian State University of Education, Ulaanbaatar 210648, Mongolia.
³ Inner Mongolia Research Institute of Traditional Mongolian Medicine Engineering Technology/College of Mongolian Medicine and Pharmacy, Inner Mongolia University for Nationalities, Tongliao 028000, China.
⁴ Inner Mongolia Key Laboratory for the Natural Products Chemistry and Functional Molecular Synthesis, College of Chemistry and Chemical Engineering, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia 028000, China.
⁵ Julius L. Chambers Biomedical Biotechnology Research Institute, Dept of Biological & Biomedical Sciences, North Carolina Central University, Kannapolis, NC 28081, USA.

Abstract

Melanoma is a serious malignant form of skin cancer. Euphorbiaceae compound B (ECB, 2,4-dihydroxy-6-methoxy-3-methylacetophenone) is an acetophenone compound that is isolated from Euphorbia ebracteolata Hayata (EEH), an herbaceous perennial, and has antitumor activity. Here, we transplanted human melanoma cells into zebrafish embryos to establish a zebrafish/melanoma model. We showed that this model can be used to evaluate the therapeutic effect of EEH and ECB and discussed its potential mechanism of action. The results showed that ECB was an active ingredient of EEH in inhibiting melanoma-induced hyperplasia of blood vessels in zebrafish embryos, similar to the angiogenic inhibitor vatalanib. ECB inhibited the number and length of subintestinal veins (p < 0.05), as well as the distribution of melanoma in zebrafish embryos (p < 0.05). More importantly, unlike vatalanib, ECB only inhibited melanoma-induced abnormal and excessive growth of blood vessels in xenografts. In addition, ECB inhibited the mRNA expression of vegfr2 and vegfr3 in zebrafish. Both vegfr2 and vegfr3 are essential genes that regulate blood vessel formation and upregulate the expression of p53 and casp3a genes in zebrafish. Together, the above-mentioned results indicate that ECB has a potential antimelanoma effect in vivo, which may be mediated by inhibiting vascular endothelial growth factor receptors.