farnesyl-pyrophosphate and Glioblastoma

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.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Survival; Diphosphonates; Drug Synergism; Flow Cytometry; Geranyltranstransferase; Glioblastoma; Humans; JNK Mitogen-Activated Protein Kinases; Mevalonic Acid; Paclitaxel; Pamidronate; Polyisoprenyl Phosphates; Sesquiterpenes; Signal Transduction; Time Factors; Tumor Suppressor Protein p53