Farnesyl diphosphate synthase attenuates paclitaxel-induced apoptotic cell death in human glioblastoma U87MG cells.

Abstract

Increased expression of farnesyl diphosphate synthase (FPPS) by stable transfection appeared to attenuate paclitaxel-induced apoptotic cell death in human glioblastoma U87MG cells. The present results suggest that the apoptotic functions of p53 and c-Jun N-terminal kinase (JNK) are affected by FPPS. Farnesyl diphosphate, a catalytic product of FPPS, also attenuated mentioned paclitaxel-induced apoptotic cell death. As expected, the FPPS inhibitor, pamidronate, enhanced paclitaxel-induced apoptotic cell death. The present results suggest that FPPS plays an important role in apoptotic cell death of cancer cells by blocking the JNK signaling cascade and activating mevalonate metabolism in paclitaxel-treated glioblastoma cells.

• Authors: Im Sun Woo, So Young Eun, Hyo Jung Kim, Eun Sil Kang, Hye Jung Kim, Jae Heun Lee, Ki Churl Chang, Jin-Hoi Kim, Soon-Chan Hong, Han Geuk Seo
• Journal: Neuroscience letters (Neurosci Lett) Vol. 474 Issue 2 Pg. 115-20 (Apr 26 2010) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 20298756 (Publication Type: Journal Article)
• Copyright: Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Diphosphonates
• Polyisoprenyl Phosphates
• Sesquiterpenes
• Tumor Suppressor Protein p53
• farnesyl pyrophosphate
• Geranyltranstransferase
• JNK Mitogen-Activated Protein Kinases
• Pamidronate
• Paclitaxel
• Mevalonic Acid

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Diphosphonates (pharmacology)
• Drug Synergism
• Flow Cytometry (methods)
• Geranyltranstransferase (genetics, metabolism)
• Glioblastoma (pathology, physiopathology)
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Mevalonic Acid (pharmacology)
• Paclitaxel (pharmacology)
• Pamidronate
• Polyisoprenyl Phosphates (metabolism)
• Sesquiterpenes (metabolism)
• Signal Transduction (drug effects)
• Time Factors
• Tumor Suppressor Protein p53 (metabolism)