In vivo effectiveness of orlistat in the suppression of human colorectal cancer cell proliferation

Aleksandra Czumaj , Judyta Zabielska , Alicja Pakiet , Adriana Mika , Olga Rostkowska , Wojciech Makarewicz , Jarosław Kobiela , Tomasz Śledziński , Ewa Stelmańska

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.
Author Aleksandra Czumaj
Aleksandra Czumaj,,
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, Judyta Zabielska
Judyta Zabielska,,
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, Alicja Pakiet (FCh / DEA / LChER)
Alicja Pakiet,,
- Laboratory of Chemical Environmental Risks
, Adriana Mika (FCh / DEA / LChER)
Adriana Mika,,
- Laboratory of Chemical Environmental Risks
, Olga Rostkowska
Olga Rostkowska,,
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, Wojciech Makarewicz
Wojciech Makarewicz,,
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, Jarosław Kobiela
Jarosław Kobiela,,
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, Tomasz Śledziński
Tomasz Śledziński,,
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, Ewa Stelmańska
Ewa Stelmańska,,
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Journal seriesAnticancer Research, ISSN 0250-7005, (A 20 pkt)
Issue year2019
Vol39
No7
Pages3815-3822
Publication size in sheets0.5
Keywords in EnglishColorectal cancer, fatty acid synthase, orlistat, palmitate
ASJC Classification1306 Cancer Research; 2730 Oncology; 2700 General Medicine
DOIDOI:10.21873/anticanres.13531
Languageen angielski
Score (nominal)20
ScoreMinisterial score = 20.0, 24-07-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.669; WoS Impact Factor: 2017 = 1.865 (2) - 2017=1.876 (5)
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