The anti-cancer compound Nordy inhibits CXCR4-mediated production of IL-8 and VEGF by malignant human glioma cells.
The chemokine receptor CXCR4 plays an important role in tumor growth, angiogenesis and metastasis. Our previous studies showed that Nordy, a synthetic chiral compound of nordihydroguaiaretic acid, inhibited the growth and angiogenesis of various malignant tumors. In this study we examined the capacity of Nordy to regulate CXCR4-mediated production of angiogenic factors by human glioblastoma cells. We found that Nordy potently inhibited CXCR4 ligand SDF-1-induced production of IL-8 and vascular endothelial cell growth factor, two important angiogenic factors implicated in the progression of malignant tumors. Further study revealed that the effect of Nordy was attributable to its down-regulation of the expression of functional CXCR4 in glioblastoma cells. These results suggest that the anti-cancer activity of Nordy is due, at least in part, to its suppression of the chemokine receptor CXCR4 thus reducing the production of angiogenic factors by tumor cells.
Ping
Yi-fang
YF
Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
Yao
Xiao-hong
XH
Chen
Jian-hong
JH
Liu
Hong
H
Chen
Dai-lun
DL
Zhou
Xiang-dong
XD
Wang
Ji Ming
JM
Bian
Xiu-wu
XW
D000704:Analysis of Variance; D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000737:chemistry / Q000494:pharmacology / Q000031:analogs & derivatives; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000032:analysis; D019718:Receptors, CXCR4 / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D042501:Angiogenic Proteins; D000970:Antineoplastic Agents; D016209:Interleukin-8; D017705:Lignans; D016859:Lipoxygenase Inhibitors; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; C510003:nordy; D009637:Masoprocol