1. In Vivo Effectiveness of Orlistat in the Suppression of Human Colorectal Cancer Cell Proliferation
- Author
-
Judyta Zabielska, Alicja Pakiet, Tomasz Sledzinski, Adriana Mika, Jarosław Kobiela, Olga Rostkowska, Wojciech Makarewicz, Aleksandra Czumaj, and Ewa Stelmanska
- Subjects
Cancer Research ,biology ,Chemistry ,Cell growth ,Colorectal cancer ,General Medicine ,medicine.disease ,digestive system diseases ,Cell membrane ,03 medical and health sciences ,Fatty acid synthase ,Orlistat ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,In vivo ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,biology.protein ,Extracellular ,neoplasms ,medicine.drug - Abstract
Background/aim Fatty acid synthase (FASN) provides palmitate for cell membrane formation in colorectal cancer (CRC) cells, however, palmitate is also available in the blood of CRC patients. The aim of this study was to examine whether orlistat, a FASN inhibitor, is able to attenuate CRC cell growth despite the availability of extracellular palmitate. Materials and methods Palmitate concentrations were measured in serum from CRC patients and healthy controls. HT-29 CRC cells were treated with orlistat and palmitate. Results Treatment of CRC cells with orlistat caused a dose-dependent inhibition of cell proliferation. In turn, delivery of extracellular palmitate at doses lower than those found in the serum of CRC patients reversed inhibition by orlistat concentrations of up to 10 μM. Conclusion Inhibition of CRC cell proliferation by orlistat is reversed by palmitate which is present at high levels in the serum. Therefore, orlistat may be effective in vivo only at high concentrations.
- Published
- 2019