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

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.

• Authors: Maria Notarnicola, Michele Barone, Antonio Francavilla, Valeria Tutino, Giusy Bianco, Angela Tafaro, Mario Minoia, Lorenzo Polimeno, Anna Napoli, Maria Principia Scavo, Maria Gabriella Caruso
• Journal: Oncology reports (Oncol Rep) Vol. 36 Issue 2 Pg. 893-9 (Aug 2016) ISSN: 1791-2431 [Electronic] Greece
• PMID: 27277576 (Publication Type: Journal Article)

Chemical References

• Cell Cycle Proteins
• Estrogen Receptor alpha
• Estrogen Receptor beta
• Fatty Acids, Omega-3
• Gli1 protein, mouse
• Hedgehog Proteins
• Lactones
• Olive Oil
• Pes1 protein, mouse
• Proteins
• RNA-Binding Proteins
• Shh protein, mouse
• Zinc Finger Protein GLI1
• Orlistat
• Lovastatin
• Fatty Acid Synthases

Topics

• Animals
• Cell Cycle Proteins
• Cell Proliferation (drug effects, genetics)
• Disease Models, Animal
• Estrogen Receptor alpha (genetics)
• Estrogen Receptor beta (genetics)
• Fatty Acid Synthases (genetics)
• Fatty Acids, Omega-3 (administration & dosage)
• Gene Expression (drug effects)
• Hedgehog Proteins (genetics)
• Intestinal Polyps (drug therapy, genetics)
• Lactones (pharmacology)
• Lovastatin (pharmacology)
• Mice
• Olive Oil (administration & dosage)
• Orlistat
• Proteins (genetics)
• RNA-Binding Proteins
• Zinc Finger Protein GLI1 (genetics)