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

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T-Cell Leukemia
Fatty Acid Synthases
Down-Regulation
Cell Line
Growth
Neoplasms
Jurkat Cells
Biological Preservation
Fatty Acids
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Tumor Microenvironment
Cell Biology
orlistat
Signal Transduction
Cell Cycle
Obesity
Membranes
Enzymes
Therapeutics
Pharmaceutical Preparations

Keywords

  • FASN
  • leukemia
  • PD-L1

ASJC Scopus subject areas

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

Cite this

Fatty acid synthase inhibitor orlistat impairs cell growth and down-regulates PD-L1 expression of a human T-cell leukemia line. / Cioccoloni, Giorgia; Aquino, Angelo; Notarnicola, Maria; Caruso, Maria Gabriella; Bonmassar, Enzo; Zonfrillo, Manuela; Caporali, Simona; Faraoni, Isabella; Villivà, Cristina; Fuggetta, Maria Pia; Franzese, Ornella.

In: Journal of Chemotherapy, 01.01.2019.

Research output: Contribution to journalArticle

Cioccoloni, Giorgia ; Aquino, Angelo ; Notarnicola, Maria ; Caruso, Maria Gabriella ; Bonmassar, Enzo ; Zonfrillo, Manuela ; Caporali, Simona ; Faraoni, Isabella ; Villivà, Cristina ; Fuggetta, Maria Pia ; Franzese, Ornella. / Fatty acid synthase inhibitor orlistat impairs cell growth and down-regulates PD-L1 expression of a human T-cell leukemia line. In: Journal of Chemotherapy. 2019.
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