Lovastatin, but not orlistat, reduces intestinal polyp volume in an ApcMin/+ mouse model

Maria Notarnicola, Michele Barone, Antonio Francavilla, Valeria Tutino, Giusy Bianco, Angela Tafaro, Mario Minoia, Lorenzo Polimeno, Anna Napoli, Maria Principia Scavo, Maria Gabriella Caruso

Research output: Contribution to journalArticle

Abstract

The statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and orlistat, an inhibitor of fatty acid synthase (FAS), inhibit tumor cell growth by restricting cholesterol and fatty acid synthesis, respectively. We previously demonstrated that an omega (ω)-3 polyunsaturated fatty acid (PUFA)- or olive oil-enriched diet reduced the polyp number and volume in ApcMin/+ mice. This phenomenon was associated with a significant inhibition of FAS and HMGCoAR, as well as an increase in the estrogen receptor (ER)β/α ratio. Herein, we evaluated the effect of lovastatin and orlistat on polyp development and ER expression in ApcMin/+ mice, in order to confirm previous data obtained with ω-3-PUFAs and olive oil. As expected, the use of lovastatin and orlistat significantly reduced HMGCoAR and FAS enzymatic activities and gene expression in colonic tissues, but did not affect the number of intestinal polyps, while there was a statistically significant reduction in polyp volume only in the mouse group treated with lovastatin. In the mice receiving orlistat, we observed a significant increase in cell proliferation in the polyp tissue, as well as enhanced expression of ERα. Moreover, the overexpression of ERα was associated with a statistically significant increase in PES1, Shh and Gli1 protein levels, considered ERα-related molecular targets.

Original languageEnglish
Pages (from-to)893-899
Number of pages7
JournalOncology Reports
Volume36
Issue number2
DOIs
Publication statusPublished - Aug 1 2016

Keywords

  • Colon cancer
  • Estrogen receptor
  • Lipogenic enzymes
  • Lovastatin
  • Orlistat

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Notarnicola, M., Barone, M., Francavilla, A., Tutino, V., Bianco, G., Tafaro, A., Minoia, M., Polimeno, L., Napoli, A., Scavo, M. P., & Caruso, M. G. (2016). Lovastatin, but not orlistat, reduces intestinal polyp volume in an ApcMin/+ mouse model. Oncology Reports, 36(2), 893-899. https://doi.org/10.3892/or.2016.4856