RPR-115135, a new non peptidomimetic farnesyltransferase inhibitor, induces G0/G1 arrest only in serum starved cells.

Abstract

A new non peptidomimetic farnesyltransferase inhibitor, RPR-115135, was studied in an isogenic cell model system consisting of human colon cancer HCT-116 line. HCT-116 cells were transfected with an empty control pCMV vector or with a dominant-negative mutated p53 transgene to disrupt p53 function. Growth inhibitory effects of RPR-115135 were evaluated on cells growing under different conditions (serum starvation, serum starvation and recovery, nocodazole treatment). The cytotoxic activity of RPR-115135 was independent of the cell cycle status of the target cells. Addition of RPR-115135 only to cells exposed to reduced serum conditions (0.1% FCS) resulted in an enhanced ability of HCT-116 cells to arrest in the G0/G1 phase. This arrest response appeared independent of p53/p21cip1/waf-1 function. A reduction of Cyclin A protein amount by RPR-115135 was observed in both clones. These latter results suggest that RPR-115135 might down-regulate the cell cycle factor that would normally impede G0/G1 arrest.

• Authors: P Russo, C Ottoboni, A Crippa, J F Riou, P M O'Connor
• Journal: International journal of oncology (Int J Oncol) Vol. 18 Issue 4 Pg. 855-62 (Apr 2001) ISSN: 1019-6439 [Print] Greece
• PMID: 11251185 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Culture Media, Serum-Free
• Cyclins
• Enzyme Inhibitors
• Indoles
• RPR115135
• Tumor Suppressor Protein p53
• Alkyl and Aryl Transferases
• Farnesyltranstransferase
• Nocodazole

Topics

• Alkyl and Aryl Transferases (antagonists & inhibitors)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Cell Cycle (drug effects, physiology)
• Cell Survival (drug effects)
• Colonic Neoplasms (enzymology, pathology)
• Culture Media, Serum-Free (metabolism)
• Cyclins (metabolism)
• Enzyme Inhibitors (pharmacology)
• Farnesyltranstransferase
• Flow Cytometry
• Genes, p53
• Humans
• Indoles (pharmacology)
• Mutation
• Nocodazole (pharmacology)
• Tumor Cells, Cultured (drug effects)
• Tumor Suppressor Protein p53 (metabolism)