Higher farnesyl diphosphate synthase activity in human colorectal cancer inhibition of cellular apoptosis.

Maria Notarnicola, Caterina Messa, Aldo Cavallini, Maurizio Bifulco, Mario Felice Tecce, Davide Eletto, Alfredo Di Leo, Severino Montemurro, Chiara Laezza, Maria Gabriella Caruso

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Abstract

OBJECTIVE: Farnesyl diphosphate synthase (FPPs) produces FPP which is considered a branch-point intermediate in the synthesis of sterols and isoprenylated cellular metabolites. In this study we investigated whether detectable FPPs activity was present in human colorectal cancer (CRC), also evaluating in vitro the role of this enzyme in the growth and apoptosis of CRC cells by using Pamidronate (PAM), a FPPs activity inhibitor. METHODS: The activity level of FPPs was determined in CRC and the normal surrounding mucosa of 50 patients by radiochemical assay. The FPPs mRNA expression was investigated in 15 of 50 patients by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). K-ras mutation was evaluated using PCR and restriction enzyme analysis. Cell growth and apoptosis, after PAM treatment, in human CRC cell line DLD-1 were measured by MTT test and DNA fragmentation, respectively. RESULTS: FPPs activity was detectable in human CRC. FPPs activity and its mRNA were significantly more abundant in cancer samples than in normal mucosa. In vitro PAM resulted in a significant reduction of cell growth and also gave rise to a marked proapoptotic effect. CONCLUSIONS: This study provides the first evidence of the presence of FPPs activity in human CRC. Moreover, FPPs enzyme was found to play a significant role in colon cancer proliferation. Copyright (c) 2004 S. Karger AG, Basel

Original languageEnglish
Pages (from-to)351-358
Number of pages8
JournalOncology
Volume67
Issue number5-6
Publication statusPublished - 2004

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Notarnicola, M., Messa, C., Cavallini, A., Bifulco, M., Tecce, M. F., Eletto, D., Di Leo, A., Montemurro, S., Laezza, C., & Caruso, M. G. (2004). Higher farnesyl diphosphate synthase activity in human colorectal cancer inhibition of cellular apoptosis. Oncology, 67(5-6), 351-358.