Cioccoloni, G orcid.org/0000-0003-0102-9182, Aquino, A, Notarnicola, M et al. (8 more authors) (2020) Fatty acid synthase inhibitor orlistat impairs cell growth and down-regulates PD-L1 expression of a human T-cell leukemia line. Journal of Chemotherapy, 32 (1). pp. 30-40. ISSN 1120-009X
Abstract
Fatty Acid Synthase (FASN) is responsible for the de novo synthesis of fatty acids, which are involved in the preservation of biological membrane structure, energy storage and assembly of factors involved in signal transduction. FASN plays a critical role in supporting tumor cell growth, thus representing a potential target for anti-cancer therapies. Moreover, this enzyme has been recently associated with increased PD-L1 expression, suggesting a role for fatty acids in the impairment of the immune response in the tumor microenvironment. Orlistat, a tetrahydrolipstatin used for the treatment of obesity, has been reported to reduce FASN activity, while inducing a sensible reduction of the growth potential in different cancer models. We have analyzed the effect of orlistat on different features involved in the tumor cell biology of the T-ALL Jurkat cell line. In particular, we have observed that orlistat inhibits Jurkat cell growth and induces a perturbation of cell cycle along with a decline of FASN activity and protein levels. Moreover, the drug produces a remarkable impairment of PD-L1 expression. These findings suggest that orlistat interferes with different mechanisms involved in the control of tumor cell growth and can potentially contribute to decrease the tumor-associated immune-pathogenesis.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2019 Edizioni Scientifi che per l'Informazione su Farmaci e Terapia. This is an author produced version of a journal article published in the Journal of Chemotherapy. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | FASN; PD-L1; leukemia |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Environment (Leeds) > School of Food Science and Nutrition (Leeds) > FSN Chemistry and Biochemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 11 Dec 2019 11:28 |
Last Modified: | 28 Nov 2020 01:51 |
Status: | Published |
Publisher: | Taylor & Francis |
Identification Number: | 10.1080/1120009x.2019.1694761 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:154488 |