Fatty acid synthase inhibitor orlistat impairs cell growth and down-regulates PD-L1 expression of a human T-cell leukemia line

Giorgia Cioccoloni, Angelo Aquino, Maria Notarnicola, Maria Gabriella Caruso, Enzo Bonmassar, Manuela Zonfrillo, Simona Caporali, Isabella Faraoni, Cristina Villivà, Maria Pia Fuggetta, Ornella Franzese

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalJournal of Chemotherapy
DOIs
Publication statusAccepted/In press - Jan 1 2019

Keywords

  • FASN
  • leukemia
  • PD-L1

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Cioccoloni, G., Aquino, A., Notarnicola, M., Caruso, M. G., Bonmassar, E., Zonfrillo, M., Caporali, S., Faraoni, I., Villivà, C., Fuggetta, M. P., & Franzese, O. (Accepted/In press). Fatty acid synthase inhibitor orlistat impairs cell growth and down-regulates PD-L1 expression of a human T-cell leukemia line. Journal of Chemotherapy. https://doi.org/10.1080/1120009X.2019.1694761