Aleksandra Czumaj1, Judyta Zabielska2, Alicja Pakiet3, Adriana Mika3, Olga Rostkowska4, Wojciech Makarewicz5, Jarosław Kobiela4, Tomasz Sledzinski6, Ewa Stelmanska2. 1. Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland. 2. Department of Biochemistry, Faculty of Medicine, Medical University of Gdansk, Gdansk, Poland. 3. Department of Environmental Analysis, Faculty of Chemistry, University of Gdansk, Gdansk, Poland. 4. Department of General, Endocrine and Transplant Surgery, Faculty of Medicine, Medical University of Gdansk, Gdansk, Poland. 5. Department and Clinic of Surgical Oncology, Faculty of Medicine, Medical University of Gdansk, Gdansk, Poland. 6. Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland tomasz.sledzinski@gumed.edu.pl.
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. Copyright
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. Copyright
Authors: Adriana Mika; Alicja Pakiet; Aleksandra Czumaj; Zbigniew Kaczynski; Ivan Liakh; Jarek Kobiela; Adrian Perdyan; Krystian Adrych; Wojciech Makarewicz; Tomasz Sledzinski Journal: J Clin Med Date: 2020-04-12 Impact factor: 4.241