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Overexpression of the orphan receptor Nur77 and its translocation induced by PCH4 may inhibit malignant glioma cell growth and induce cell apoptosis
Author(s) -
Chang LiFu,
Lin PoCheng,
Ho LiIng,
Liu PoYen,
Wu WanChen,
Chiang IPing,
Chang HuiWen,
Lin ShinnZong,
Harn YeuChern,
Harn HorngJyh,
Chiou TzyyWen
Publication year - 2011
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.21809
Subject(s) - nerve growth factor ib , apoptosis , downregulation and upregulation , microbiology and biotechnology , annexin , cell growth , cancer research , chromosomal translocation , signal transduction , cell , chemistry , biology , biochemistry , transcription factor , nuclear receptor , gene
Background In previous study, n ‐butylidenephthalide (BP), a natural compound from Angelica sinensis , has anti‐glioblastoma multiform (GBM) cell effects. In this study, we modified BP structure to increase anti‐GBM cell effects. The anti‐GBM cell effects of one derivative of BP, (Z)‐ N ‐(2‐(dimethylamino)ethyl)‐2‐(3‐((3‐oxoisobenzofuran‐1(3H)‐ylidene)methyl)phenoxy)acetamide (PCH4) were tested in vitro and in vivo. Methods MTT assay and PI/Annexin V assay were performed to evaluate the anti‐GBM effects of PCH4. The Nur77 expression and translocation were assayed by RT‐PCR and Western blot. The Nur77 siRNA was used to downregulate the Nur77 expression. The JNK inhibitor (SP600125) was used to block the JNK pathway. Results The anti‐GBM effect of PCH4 is four times more than BP. The IC 50 of PCH4 on DBTRG‐05MG cells was 50 µg/ml. Nur77 expression and translocation from the nucleus to the cytoplasm were important in PCH4‐induced apoptosis. Furthermore, the downregulation of PCH4‐induced Nur77 expression by Nur77 siRNA reduced PCH4‐induced apoptosis. In addition, PCH4‐induced apoptosis was associated with the JNK pathway. The JNK inhibitor, SP600125, inhibited Nur77 mRNA expression and reduced PCH4‐induced apoptosis. Conclusions In conclusion, PCH4, a derivative of BP, induced Nur77‐mediated apoptosis via the JNK pathway and this mechanism, which is different from that of BP, may explain the increase in the anti‐tumor effects on GBM. J. Surg. Oncol. 2011; 103:442–450. © 2011 Wiley‐Liss, Inc.