In vitro anti-invasive effects of N-(4-hydroxyphenyl)-retinamide on human prostatic adenocarcinoma.

Abstract

Components of malignant invasion, namely cellular adhesion, motility, and proteolytic capability provide potential sites of pharmacological intervention for malignancy. In this study, a series of experiments were performed to examine the effects of N-(4-hydroxyphenyl) retinamide (4-HPR, Fenretinide) on cellular adhesion, motility and proteolytic activity of established prostate cancer cell lines, TSU-PR 1 and PC-3. Radioadhesion study showed that the treatment of TSU-PR 1 and PC-3 cells with 10(-6) M of 4-HPR resulted in a 32% and 37% reduction (p < 0.05), respectively, in the cellular adhesion to the matrigel extract. Radiomigration assay also demonstrated that 4-HPR concentration of 10(-6) M reduced the cellular motility by 29% in TSU-PR1 and 28% in PC-3 cells (p < 0.05). Spectrolyse PL indirect chromogenic assay revealed an increase in total activatable uPA activity (TSU-PR 1: 25%, PC-3: 32%, P < 0.05), while Spectrolyse UK direct assay demonstrated a mild, but a statistically significant reduction (PC-3: 5%, TSU-PR1: 9%, P < 0.05) in active uPA activity. Northern analysis and ELISA assays showed that 4-HPR at 10(-6) M enhances the expression of type 1 plasminogen activator inhibitor (PAI-1). Type IV collagenase western blot analysis and densitometry did not demonstrate suppression of the enzyme secretion, but in fact suggested increased translation of the enzyme when treated with 10(-6) M concentration of fenretinide. The results of this study demonstrate that 4-HPR inhibits in vitro cellular adhesion and motility of human prostate adenocarcinoma cell lines, TSU-PR1 and PC-3. Additionally, uPA and PAI-1 assay results suggest that 4-HPR may impair active uPA's proteolytic activity while upregulating the expression of total activatable uPA and PAI-1. The results of this study therefore support 4-HPR's role as a potential anti-invasive agent.

• Authors: J H Kim, T Tanabe, G W Chodak, D B Rukstalis
• Journal: Anticancer research (Anticancer Res) 1995 Jul-Aug Vol. 15 Issue 4 Pg. 1429-34 ISSN: 0250-7005 [Print] Greece
• PMID: 7654032 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Plasminogen Activator Inhibitor 1
• RNA, Messenger
• Fenretinide
• Urokinase-Type Plasminogen Activator
• Collagenases
• Matrix Metalloproteinase 9

Topics

• Adenocarcinoma (drug therapy, pathology)
• Cell Adhesion (drug effects)
• Cell Movement (drug effects)
• Collagenases (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Fenretinide (pharmacology)
• Humans
• Male
• Matrix Metalloproteinase 9
• Neoplasm Invasiveness
• Plasminogen Activator Inhibitor 1 (analysis, genetics)
• Prostatic Neoplasms (drug therapy, pathology)
• RNA, Messenger (analysis)
• Tumor Cells, Cultured
• Urokinase-Type Plasminogen Activator (metabolism)