680
Views
16
CrossRef citations to date
0
Altmetric
Anticancer Original Research Papers

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

, , , , , ORCID Icon, , , , & show all
Pages 30-40 | Received 15 Apr 2019, Accepted 25 Oct 2019, Published online: 28 Nov 2019

References

  • Ritchie MK, Johnson LC, Clodfelter JE, Pemble CW, Fulp BE, Furdui CM, et al. Crystal structure and substrate specificity of human thioesterase 2: insights into the molecular basis for the modulation of fatty acid synthase. J Biol Chem. 2016;291:3520–3530.
  • Wakil SJ. Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry. 1989;28:4523–4530.
  • Hopperton KE, Duncan RE, Bazinet RP, Archer MC. Fatty acid synthase plays a role in cancer metabolism beyond providing fatty acids for phospholipid synthesis or sustaining elevations in glycolytic activity. Exp Cell Res. 2014;320:302–310.
  • Bauerschlag DO, Maass N, Leonhardt P, Verburg FA, Pecks U, Zeppernick F, et al. Fatty acid synthase overexpression: target for therapy and reversal of chemoresistance in ovarian cancer. J Transl Med. 2015;13:146.
  • Buckley D, Duke G, Heuer TS, O'Farrell M, Wagman AS, McCulloch W, et al. Fatty acid synthase - Modern tumor cell biology insights into a classical oncology target. Pharmacol Ther. 2017;177:23–31.
  • Bhatt AP, Jacobs SR, Freemerman AJ, Makowski L, Rathmell JC, Dittmer DP, et al. Dysregulation of fatty acid synthesis and glycolysis in non-Hodgkin lymphoma. PNAS. 2012;109:11818–11823.
  • Cai Y, Wang J, Zhang L, Wu D, Yu D, Tian X, et al. Expressions of fatty acid synthase and HER2 are correlated with poor prognosis of ovarian cancer. Med Oncol. 2015;32:391.
  • Mashima T, Seimiya H, Tsuruo T. De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. Br J Cancer. 2009;100:1369–1372.
  • Zhao Y, Butler EB, Tan M. Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis. 2013;4:e532.
  • Wang H, Xi Q, Wu G. Fatty acid synthase regulates invasion and metastasis of colorectal cancer via Wnt signaling pathway. Cancer Med. 2016;5:1599–1606.
  • Liu ZL, Zhou Y, Luo QF, Hu M, Wang G, Huang S, et al. Inhibition of fatty acid synthase suppresses osteosarcoma cell invasion and migration. Indian J Pathol Microbiol. 2012;55:163–169.
  • Grube S, Dünisch P, Freitag D, Klausnitzer M, Sakr Y, Walter J, et al. Overexpression of fatty acid synthase in human gliomas correlates with the WHO tumor grade and inhibition with Orlistat reduces cell viability and triggers apoptosis. J Neurooncol. 2014;118:277–287.
  • Martel PM, Bingham CM, McGraw CJ, Baker CL, Morganelli PM, Meng ML, et al. S14 protein in breast cancer cells: direct evidence of regulation by SREBP-1c, superinduction with progestin, and effects on cell growth. Exp Cell Res. 2006;312:278–288.
  • Schcolnik-Cabrera A, Chávez-Blanco A, Domínguez-Gómez G, Taja-Chayeb L, Morales-Barcenas R, Trejo-Becerril C, et al. Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy. Expert Opin Investig Drugs. 2018;27:475–489.
  • Sankaranarayanapillai M, Zhang N, Baggerly KA, Gelovani JG. Metabolic shifts induced by fatty acid synthase inhibitor orlistat in non-small cell lung carcinoma cells provide novel pharmacodynamic biomarkers for positron emission tomography and magnetic resonance spectroscopy. Mol Imaging Biol. 2013;15:136–147.
  • Agostini M, Almeida LY, Bastos DC, Ortega RM, Moreira FS, Seguin F, et al. The fatty acid synthase inhibitor orlistat reduces the growth and metastasis of orthotopic tongue oral squamous cell carcinomas. Mol Cancer Ther. 2014;13:585–595.
  • Huang HQ, Tang J, Zhou ST, Yi T, Peng HL, Shen GB, et al. Orlistat, a novel potent antitumor agent for ovarian cancer: proteomic analysis of ovarian cancer cells treated with Orlistat. Int J Oncol. 2012; 41:523–532.
  • Seguin F, Carvalho MA, Bastos DC, Agostini M, Zecchin KG, Alvarez-Flores MP, et al. The fatty acid synthase inhibitor orlistat reduces experimental metastases and angiogenesis in B16-F10 melanomas. Br J Cancer. 2012;107:977–987.
  • Cioccoloni G, Bonmassar L, Pagani E, Caporali S, Fuggetta MP, Bonmassar E, et al. Influence of fatty acid synthase inhibitor orlistat on the DNA repair enzyme O6-methylguanine-DNA methyltransferase in human normal or malignant cells in vitro. Int J Oncol. 2015;47:764–772.
  • Pemble CWT, Johnson LC, Kridel SJ, Lowther WT. Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by orlistat. Nat Struct Mol Biol. 2007;14:704–709.
  • Knowles LM, Yang C, Osterman A, Smith JW. Inhibition of fatty-acid synthase induces caspase-8-mediated tumor cell apoptosis by up-regulating DDIT4. J Biol Chem. 2008;283:31378–31384.
  • Knowles LM, Axelrod F, Browne CD, Smith JW. A fatty acid synthase blockade induces tumor cell-cycle arrest by down-regulating Skp2. J Biol Chem. 2004;279:30540–30545.
  • Shen M, Tsai Y, Zhu R, Keng PC, Chen Y, Chen Y, et al. FASN-TGF-β1-PD-L1 axis contributes to the development of resistance to NK cell cytotoxicity of cisplatin-resistant lung cancer cells. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863:313–322.
  • Liu H, Liu Y, Zhang JT. A new mechanism of drug resistance in breast cancer cells: fatty acid synthase overexpression-mediated palmitate overproduction. Mol. Cancer Ther. 2008;7:263–270.
  • Sun C, Mezzadra R, Schumacher TN. Regulation and function of the PD-L1 checkpoint. Immunity. 2018;48:434–452.
  • Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol. 2017;8:561.
  • Franzese O, Torino F, Fuggetta MP, Aquino A, Roselli M, Bonmassar E, et al. Tumor immunotherapy. drug-induced neoantigens (xenogenization) and immune checkpoint inhibitors. Oncotarget. 2017;8:41641–41669.
  • Goods BA, Hernandez AL, Lowther DE, Lucca LE, Lerner BA, Gunel M, et al. Functional differences between PD-1+ and PD-1- CD4+ effector T cells in healthy donors and patients with glioblastoma multiforme. PLoS ONE. 2017;12:e0181538.
  • Gong J, Chehrazi-Raffle A, Reddi S, Salgia R. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J Immunother Cancer. 2018;6:8.
  • Renner K, Singer K, Koehl GE, Geissler EK, Peter K, Siska PJ, et al. Metabolic hallmarks of tumor and immune cells in the tumor microenvironment. Front Immunol. 2017;8:248.
  • Kouidhi S, Ayed BF, Benammar Elgaaied A. Targeting Tumor Metabolism: A New Challenge to Improve Immunotherapy. Front Immunol. 2018; 9:353.
  • Pallasch CP, Schwamb J, Königs S, Schulz A, Debey S, Kofler D, et al. Targeting lipid metabolism by the lipoprotein lipase inhibitor orlistat results in apoptosis of B-cell chronic lymphocytic leukemia cells. Leukemia. 2008;22:585–592.
  • Norberg M, Lindhagen E, Kanduri M, Rickardson L, Sundström C, Stamatopoulos K, et al. Screening for cytotoxic compounds in poor-prognostic chronic lymphocytic leukemia. Anticancer Res. 2012;32:3125–3136.
  • Goldberg JM, Silverman LB, Levy DE, Dalton VK, Gelber RD, Lehmann L, et al. Childhood T-cell acute lymphoblastic leukemia: the Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience. JCO. 2003;21:3616–3622.
  • Oudot C, Auclerc MF, Levy V, Porcher R, Piguet C, Perel Y, et al. Prognostic factors for leukemic induction failure in children with acute lymphoblastic leukemia and outcome after salvage therapy: the FRALLE 93 study. JCO. 2008;26:1496–1503.
  • Cervantes-Madrid D, Dueñas-González A. Antitumor effects of a drug combination targeting glycolysis, glutaminolysis and de novo synthesis of fatty acids. Oncol Rep. 2015;34:1533–1542.
  • Sadowski MC, Pouwer RH, Gunter JH, Lubik AA, Quinn RJ, Nelson CC. The fatty acid synthase inhibitor triclosan: repurposing an anti-microbial agent for targeting prostate cancer. Oncotarget. 2014;5:9362–9381.
  • Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984;22:27–55.
  • Bonmassar L, Fossile E, Scoppola A, Graziani G, Prete SP, Formica V, et al. Detection of circulating tumor cells is improved by drug-induced antigen up-regulation: preclinical and clinical studies. Anticancer Res. 2010;30:4721–4730.
  • Heuer TS, Ventura R, Mordec K, Lai J, Fridlib M, Buckley D, et al. FASN inhibition and taxane treatment combine to enhance anti-tumor efficacy in diverse xenograft tumor models through disruption of tubulin palmitoylation and microtubule organization and FASN inhibition-mediated effects on oncogenic signaling and gene expression. EBioMedicine. 2017; 16:51–62.
  • Sever R, Brugge JS. Signal transduction in cancer. Cold Spring Harbor Perspect Med. 2015; 5:a006098.
  • Corominas-Faja B, Vellon L, Cuyàs E, Buxó M, Martin-Castillo B, Serra D, et al. Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer. Histol Histopathol. 2017;32:687–698.
  • Jones SF, Infante JR. Molecular pathways: fatty acid synthase. Clin Cancer Res. 2015; 21:5434–5438.
  • Zhi J, Melia AT, Funk C, Viger-Chougnet A, Hopfgartner G, Lausecker B, et al. Metabolic profiles of minimally absorbed orlistat in obese/overweight volunteers. J Clin Pharmacol. 1996; 36:1006–1011.
  • Paulmurugan R, Bhethanabotla R, Mishra K, Devulapally R, Foygel K, Sekar TV, et al. Folate receptor-targeted polymeric micellar nanocarriers for delivery of orlistat as a repurposed drug against triple-negative breast cancer. Mol Cancer Ther. 2016;15:221–231.
  • Czumaj A, Zabielska J, Pakiet A, Mika A, Rostkowska O, Makarewicz W, et al. Vivo effectiveness of orlistat in the suppression of human colorectal cancer cell proliferation. Anticancer Res. 2019; 39:3815–3822.
  • Little JL, Wheeler FB, Koumenis C, Kridel SJ. Disruption of crosstalk between the fatty acid synthesis and proteasome pathways enhances unfolded protein response signaling and cell death. Mol Cancer Ther. 2008;7:3816–3824.
  • Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T, et al. Chemotherapy induces programmed cell death-ligand 1 overexpression via the nuclear factor-κB to foster an immunosuppressive tumor microenvironment in ovarian cancer. Cancer Res. 2015;75:5034–5045.
  • Van Der Kraak L, Goel G, Ramanan K, Kaltenmeier C, Zhang L, Normolle DP, et al. 5-Fluorouracil upregulates cell surface B7-H1 (PD-L1) expression in gastrointestinal cancers. J Immunother Cancer. 2016;4:65.
  • Ock CY, Kim S, Keam B, Kim S, Ahn YO, Chung EJ, et al. Changes in programmed death-ligand 1 expression during cisplatin treatment in patients with head and neck squamous cell carcinoma. Oncotarget. 2017;8:97920–97927.
  • Korde LA, Lusa L, McShane L, Lebowitz PF, Lukes L, Camphausen K, et al. Gene expression pathway analysis to predict response to neoadjuvant docetaxel and capecitabine for breast cancer. Breast Cancer Res Treat. 2010;119:685–699.
  • Dong L, Lv H, Li W, Song Z, Li L, Zhou S, et al. Co-expression of PD-L1 and p-AKT is associated with poor prognosis in diffuse large B-cell lymphoma via PD-1/PD-L1 axis activating intracellular AKT/mTOR pathway in tumor cells. Oncotarget. 2016;7:33350–33362.
  • Muenst S, Schaerli AR, Gao F, Däster S, Trella E, Droeser RA, et al. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2014;146:15–24.
  • Kollmann D, Ignatova D, Jedamzik J, Chang YT, Jomrich G, Baierl A, et al. PD-L1 expression is an independent predictor of favorable outcome in patients with localized esophageal adenocarcinoma. Oncoimmunology. 2018;7:e1435226.
  • Knaus HA, Kanakry CG, Luznik L, Gojo I. Immunomodulatory drugs: immune checkpoint agents in acute leukemia. CDT. 2017;18:315–331.
  • Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8:793–800.
  • Clark CA, Gupta H, Sareddy GR, Pandeswara S, Lao S, Yuan B, et al. Tumor-intrinsic PD-L1 signals regulate cell growth, pathogenesis and autophagy in ovarian cancer and melanoma. Cancer Res. 2016;76:6964–6974.
  • Yan F, Pang J, Peng Y, Molina JR, Yang P, Liu S. Elevated cellular PD1/PD-L1 expression confers acquired resistance to cisplatin in small cell lung cancer cells. PLoS One. 2016;11:e0162925.
  • Lastwika KJ, Wilson W, Li QK, Norris J, Xu H, Ghazarian SR, et al. Control of PD-L1 expression by oncogenic activation of the AKT-mTOR Pathway in non-small cell lung cancer. Cancer Res. 2016;76:227–238.
  • Li L, Pilo GM, Li X, Cigliano A, Latte G, Che L, et al. Inactivation of fatty acid synthase impairs hepatocarcinogenesis driven by AKT in mice and humans. J Hepatol. 2016;64:333–341.
  • Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.
  • Pitroda SP, Stack ME, Liu GF, Song SS, Chen L, Liang H, et al. JAK2 inhibitor SAR302503 abrogates PD-L1 expression and targets therapy-resistant non-small cell lung cancers. Mol Cancer Ther. 2018;17:732–739.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.