Targeting of epidermal growth factor receptor by cyclopentenone prostaglandin 15-Deoxy-Δ^12,14-prostaglandin J₂ in human oral squamous carcinoma cells

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• 作者：Siavash ; Hessam ; Nikitakis ; Nikolaos G. ; Sauk ; John J.
• 关键词：Cyclopentenone ; 15d-PGJ₂ ; Epidermal growth factor receptor ; Oral squamous cell carcinoma
• 刊名：Cancer Letters
• 出版年：2004
• 出版时间：July 28, 2004
• 年：2004
• 卷：211
• 期：1
• 页码：97-103
• 全文大小：250 K

文摘

Antineoplastic properties of cyclopentenone 15-deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂) involve peroxisome proliferator-activated receptor gamma (PPARγ) 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 PPARγ 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 PPARγ 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.