title: 2-Naphthoic acid ergosterol ester, an ergosterol derivative, exhibits anti-tumor activity by promoting apoptosis and inhibiting angiogenesis.
abstract: Phytosterol is a natural component of vegetable oil and includes ergosterol (ER) and β-sitosterol. In this study, three new ergosterol monoester derivatives were obtained from the reflux reaction with ergosterol, organic acids (furoic acid, salicylic acid, and 2-naphthoic acid), EDCI, and DMAP in dichloromethane. The chemical structures were defined by IR and NMR. On the basis of the results, 2-naphthoic acid ergosterol ester (NE) had the highest tumor inhibition rate and was selected to study anti-tumor activity and its mechanism at doses of 0.025mmol/kg and 0.1mmol/kg in H22-tumor bearing mice. Compared with ER, NE exhibited more stronger anti-tumor activity in vivo. Furthermore, biochemical parameters of ALT, AST, BUN, and CRE showed that NE had little toxicity to mice. NE significantly improved serum cytokine levels of IFN-γ and decreased VEGF levels. Moreover, H&E staining, TUNEL assay, immunohistochemistry, and western blotting indicated that NE exhibited anti-tumor activity in vivo by promoting apoptosis and inhibiting angiogenesis. In brief, the present study provided a method to improve ER anti-tumor activity and a reference for a new anti-tumor agent.
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agriculture University, Changchun, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Lin
authors.affiliation: Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agriculture University, Changchun, China. Electronic address: zhaoyan@jlau.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agriculture University, Changchun, China.
authors.forename: Enbo
authors.initials: E
authors.lastname: Cai
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agriculture University, Changchun, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agriculture University, Changchun, China.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agriculture University, Changchun, China.
authors.forename: Shuangli
authors.initials: S
authors.lastname: Liu
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agriculture University, Changchun, China.
authors.forename: He
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agriculture University, Changchun, China.
authors.forename: Lianxue
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agriculture University, Changchun, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Tang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; C000619277:ergosteryl 2-naphthoate; D007371:Interferon-gamma; D004875:Ergosterol
keywords: Anti-tumor activity in vivo; Ergosterol monoester derivatives; H&E; Immunohistochemistry; TUNEL; Western blot