title: The effect of benzyl isothiocyanate and its computer-aided design derivants targeting alkylglycerone phosphate synthase on the inhibition of human glioma U87MG cell line.
abstract: Benzyl isothiocyanate (BITC) has been shown to have inhibitory potential for human glioma U87MG cells; however, the effect and mechanism were not fully clear. In the present study, we found that BITC could inhibit U87MG cell proliferation, adhesion, invasion, and vasculogenic mimicry (VM) formation potential and induce oxidative stress, apoptosis, and cell cycle arrest. We also found that the expression of proliferation, invasion, VM oxidative stress, apoptosis, and cell cycle-related gene and the activity of tumor-related signaling pathways, including protein kinase C (PKC) ζ and Akt/nuclear factor-kappa B (NF-κB) pathways, were suppressed by BITC treatment. We also explored the anti-tumor potential of BITC in vivo, and we found that BITC also could regulate the expression of tumor-related gene and angiogenesis in nude mice model. Finally, we optimized the BITC construction targeting alkylglycerone phosphate synthase (AGPS) by computer-aided design, and the derivants also showed anti-tumor potential in vitro.
authors.affiliation: Department of Clinical Laboratory, Tianjin Huan Hu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin, 300060, People's Republic of China, zhuyutj@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.forename: Anmin
authors.initials: A
authors.lastname: Liu
authors.forename: Xuebin
authors.initials: X
authors.lastname: Zhang
authors.forename: Lisha
authors.initials: L
authors.lastname: Qi
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage*; D051379:Mice; D023041:Xenograft Model Antitumor Assays
chemical_list: D017879:Isothiocyanates; C031403:benzyl isothiocyanate; D019883:Alkyl and Aryl Transferases; C019654:alkylglycerone-phosphate synthase