Down-regulation of 20-HETE synthesis and signaling inhibits renal adenocarcinoma cell proliferation and tumor growth.

Abstract

BACKGROUND:

We examined the ability of inhibitors of the synthesis or actions of 20-HETE, metabolite of arachidonic acid, to inhibit proliferation of human renal carcinoma cell lines.

MATERIALS AND METHODS:

786-O and 769-P cells were exposed to either 10 microM HET0016 (selective inhibitor of 20-HETE synthesis), 10 microM WIT002 (20-HETE antagonist), or vehicle. Subsequently, we assessed the effect of WIT002 on tumor growth in vivo using an ectopic mouse model of clear-cell renal carcinoma.

RESULTS:

Addition of HET0016 and WIT002 inhibited the proliferation of 786-O and 769-P human renal cell carcinoma lines. HET0016 and WIT002 had little effect on the proliferation of primary cultures of normal human proximal tubule epithelial cells. WIT002 (10 mg/kg, s.c.) administered daily to athymic nude mice implanted subcutaneously with 786-O cells reduced the growth of the tumors by 84 % compared to vehicle (p<0.001).

CONCLUSION:

20-HETE is required for proliferation of human renal epithelial cancer.

• Authors: Anna Alexanian, Victoriya A Rufanova, Bradley Miller, Averia Flasch, Richard J Roman, Andrey Sorokin
• Journal: Anticancer research (Anticancer Res) Vol. 29 Issue 10 Pg. 3819-24 (Oct 2009) ISSN: 1791-7530 [Electronic] Greece
• PMID: 19846914 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Amidines
• HET0016
• Hydroxyeicosatetraenoic Acids
• RNA, Messenger
• TNF-Related Apoptosis-Inducing Ligand
• Arachidonic Acid
• 20-hydroxy-5,8,11,14-eicosatetraenoic acid
• Cytochrome P-450 Enzyme System
• Cytochrome P450 Family 4
• CYP4F2 protein, human
• CYP4F3 protein, human

Topics

• Amidines (pharmacology)
• Animals
• Arachidonic Acid (metabolism)
• Carcinoma, Renal Cell (drug therapy, metabolism, pathology)
• Cell Growth Processes (drug effects, physiology)
• Cytochrome P-450 Enzyme System (biosynthesis, genetics)
• Cytochrome P450 Family 4
• Down-Regulation (drug effects)
• Humans
• Hydroxyeicosatetraenoic Acids (antagonists & inhibitors, biosynthesis, pharmacology)
• Kidney Neoplasms (drug therapy, metabolism, pathology)
• Mice
• Mice, Nude
• RNA, Messenger (biosynthesis, genetics)
• TNF-Related Apoptosis-Inducing Ligand (pharmacology)
• Xenograft Model Antitumor Assays