Targeting of epidermal growth factor receptor by cyclopentenone prostaglandin 15-Deoxy-Delta12,14-prostaglandin J2 in human oral squamous carcinoma cells.
Antineoplastic properties of cyclopentenone 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) involve peroxisome proliferator-activated receptor gamma (PPARgamma) dependent and independent mechanisms. We recently reported that 15d-PGJ2 inhibits cell growth and induces apoptosis in human oral squamous cell carcinoma (SCC) partly independent of PPARgamma activation. Given the importance of epidermal growth factor receptor (EGFR) as a therapeutic target in head and neck SCC, we addressed the effects of 15d-PGJ2 on EGFR expression. 15d-PGJ2, but not other PPARgamma ligands, abrogated EGFR protein expression in oral SCC cells. 15d-PGJ2 also decreased EGFR mRNA, indicating downmodulation at the transcriptional level. Moreover, treatment with 9,10-dihydro-15d-PGJ2, a 15d-PGJ2 analog lacking the reactive carbonyl group, failed to effect EGFR expression. These findings provide evidence for EGFR downregulation in oral SCC cells through a novel anticancer effect of 15d-PGJ2 that is attributed to the reactive cyclopentenone ring system.
Siavash
Hessam
H
Department of Biomedical Sciences, Dental School, University of Maryland, Baltimore, MD 21201, USA. hsiav001@umaryland.edu
Nikitakis
Nikolaos G
NG
Sauk
John J
JJ
D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003517:Cyclopentanes / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects*; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D003517:Cyclopentanes; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D066246:ErbB Receptors; C013905:cyclopentenone; D015230:Prostaglandin D2