Nordy, a synthetic lipoxygenase inhibitor, inhibits the expression of formylpeptide receptor and induces differentiation of malignant glioma cells.
We recently found that formylpeptide receptor (FPR), a G-protein-coupled receptor that mediates chemotaxis of phagocytic leukocytes induced by bacterial peptide N-formyl-methionyl-leucyl-phenylalanine, is expressed by malignant human glioma cells and promotes tumor growth and angiogenesis. In this study, we examined the effect of Nordy, a novel chiral lipoxygenase inhibitor which was synthesized based on the structure of a natural nordihydroguaiaretic acid, on the expression of FPR by human glioblastoma cells. We found that FPR was expressed at the protein level by highly malignant human glioma cell lines U87 and BT325, and a rat glioma cell line C6. The expression level of FPR was correlated with the degree of the malignancy of tumor cells. The poorly differentiated glioma cell line U87 expressed the highest level of FPR. In U87 glioma cells, the expression of FPR was attenuated at the protein level by Nordy treatment for 48 (P<0.05). Nordy did not affect FPR mRNA expression in U87 cells. In addition, Nordy treatment seemed to promote glioma cell differentiation, as evidenced by their reduced expression of vimentin and increased expression of GFAP. Our results suggest that Nordy was capable of reducing the level of malignancy of glioma cells.
Chen
Jian-Hong
JH
Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Bian
Xiu-Wu
XW
Yao
Xiao-Hong
XH
Gong
Wanghua
W
Hu
Jinyue
J
Chen
Keqiang
K
Iribarren
Pablo
P
Zhao
Wen
W
Zhou
Xiang-Dong
XD
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D017705:Lignans / Q000008:administration & dosage*; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage*; D009637:Masoprocol / Q000031:analogs & derivatives; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000378:metabolism*
D000970:Antineoplastic Agents; D017705:Lignans; D016859:Lipoxygenase Inhibitors; D044042:Receptors, Formyl Peptide; C510003:nordy; D009637:Masoprocol