The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer
[en] Lung cancer is the leading cause of cancer deaths in the
United States. Current therapies are inadequate. Histone
deacetylase inhibitors (HDACi) are a recently developed
class of anticancer agents that cause increased acetylation
of core histones and nonhistone proteins leading to
modulation of gene expression and protein activityin -
volved in cancer cell growth and survival pathways.
We examined the efficacyof the HDACi panobinostat
(LBH589) in a wide range of lung cancers and mesotheliomas.
Panobinostat was cytotoxic in almost all 37 cancer
cell lines tested. IC50 and LD50 values were in the
low nmol/L range (4–470 nmol/L; median, 20 nmol/L).
Small cell lung cancer (SCLC) cell lines were among
the most sensitive lines, with LD50 values consistently
<25 nmol/L. In lung cancer and mesothelioma animal
models, panobinostat significantlyde creased tumor
growth byan average of 62% when compared with vehicle
control. Panobinostat was equallye ffective in
immunocompetent and severe combined immunodeficiencymic
e, indicating that the inhibition of tumor growth by
panobinostat was not due to direct immunologic effects.Panobinostat was, however, particularlyeffective in SCLC
xenografts, and the addition of the chemotherapyag ent
etoposide augmented antitumor effects. Protein analysis
of treated tumor biopsies revealed elevated amounts of cell
cycle regulators such as p21 and proapoptosis factors,
such as caspase 3 and 7 and cleaved poly[ADP-ribose] polymerase,
coupled with decreased levels of antiapoptotic
factors such as Bcl-2 and Bcl-XL. These studies together
suggest that panobinostat maybe a useful adjunct in the
treatment of thoracic malignancies, especiallySCLC.
Disciplines :
Oncology
Author, co-author :
Crisanti, Cecilia
Wallace, Africa
Kapoor, Veena
Vandermeers, Fabian ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Dowling, Melissa
Pereira, Luana
Coleman, Kara
Campling, Barbara
Fridlender, Zvi
Kao, Gary
Albelda, Steven
Language :
English
Title :
The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer
Publication date :
August 2009
Journal title :
Molecular Cancer Therapeutics
ISSN :
1535-7163
eISSN :
1538-8514
Publisher :
American Association for Cancer Research, Inc. (AACR), Philadelphia, United States - Pennsylvania
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006;24:4539-44.
Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 2006;6:38-50.
Verheul HM, Salumbides B, Van Erp K, et al. Combination strategy targeting the hypoxia inducible factor-1 alpha with mammalian target of rapamycin and histone deacetylase inhibitors. Clin Cancer Res 2008;14:3589-97.
Haefner M, Bluethner T, Niederhagen M, et al. Experimental treatment of pancreatic cancer with two novel histone deacetylase inhibitors. World J Gastroenterol 2008;14:3681-92.
Zhou Q, Agoston AT, Atadja P, Nelson WG, Davidson NE. Inhibition of histone deacetylases promotes ubiquitin-dependent proteasomal degradation of DNA methyltransferase 1 in human breast cancer cells. Mol Cancer Res 2008;6:873-83.
Giles F, Fischer T, Cortes J, et al. A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies. Clin Cancer Res 2006;12:4628-35.
Ellis L, Pan Y, Smyth GK, et al. Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profiles in cutaneous T-cell lymphoma. Clin Cancer Res 2008;14:4500-10.
Li Q, Verschraegen CF, Mendoza J, Hassan R. Cytotoxic activity of the recombinant anti-mesothelin immunotoxin, SS1(dsFv)PE38, towards tumor cell lines established from ascites of patients with peritoneal mesotheliomas. Anticancer Res 2004;24:1327-35.
Jackaman C, Bundell CS, Kinnear BF, et al. IL-2 intratumoral immunotherapy enhances CD8+ T cells that mediate destruction of tumor cells and tumor-associated vasculature: a novel mechanism for IL-2. J Immunol 2003;171:5051-63.
Davis MR, Manning LS, Whataker D, Garlepp MJ, Robinson BWS. Establishment of a murine model of malignant mesotheoioma. Int J Cancer 1992;52:881-86.
Lin KY, Guarnieri FG, Staveley-O'Carroll KF, et al. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigens. Cancer Res 1996;56:21-26.
Wilderman M, Sun J, Khan M, et al. Intrapulmonary interferon-β gene therapy using an adenoviral vector is highly effective in a murine orthotopic model of lung adenocarcinoma via a combination of direct toxicity, NK cell, and CD8 T-cell mediated effects. Cancer Res 2005;65:8379-87.
Campling BG, Haworth AC, Baker HM, et al. Establishment and characterization of a panel of human lung cancer cell lines. Cancer 1992;69:2064-74.
Kao GD, McKenna WG, Guenther MG, Muschel RJ, Lazar MA, Yen TJ. Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response. J Cell Biol 2003;160:1017-27.
Tsai SC, Valkov N, Yang WM, Gump J, Sullivan D, Seto E. Histone deacetylase interacts directly with DNA topoisomerase II. Nat Genet 2000;26:349-53.
Kim MS, Blake M, Baek JH, Kohlhagen G, Pommier Y, Carrier F. Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA. Cancer Res 2003;63:7291-300.
Rundall BK, Denlinger CE, Jones DR. Suberoylanilide hydroxamic acid combined with gemcitabine enhances apoptosis in non-small cell lung cancer. Surgery 2005;138:360-7.
Neuzil J, Swettenham E, Gellert N. Sensitization of mesothelioma to TRAIL apoptosis by inhibition of histone deacetylase: role of Bcl-xL downregulation. Biochem Biochem Res Commun 2004;314:186-91.
Miyanaga A, Gemma A, Noro R, et al. Antitumor activity of histone deacetylase inhibitors in non-small cell lung cancer cells: development of a molecular predictive model. Mol Cancer Ther 2008;7:1923-30.
Komatsu N, Kawamata N, Takeuchi S, et al. SAHA, a HDAC inhibitor, has profound anti-growth activity against non-small cell lung cancer cells. Oncol Rep 2006;15:187-91.
Fournel M, Bonfils C, Hou Y, et al. MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectruman titumor activity in vitro and in vivo. Mol Cancer Ther 2008;7:759-68.
Platta CS, Greenblatt DY, Kunnimalaiyaan M, Chen H. The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. JSR 2007;142:219-26.
Hajji N, Wallenborg K, Vlachos P, Nyman U, Hermanson O, Joseph B. Combinatorial action of the HDAC inhibitor trichostatin A and etoposide induces caspase-mediated AIF-dependent apoptotic cell death in non-small cell lung carcinoma cells. Oncogene 2008;27:3134-44.
Kim HR, Kim EJ, Yang SH, et al. Trichostatin A induces apoptosis in lung cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway? Exp Mol Med 2006;38:616-24.
Choi YH. Induction of apoptosis by trichostatin A, a histone deacetylase inhibitor, is associated with inhibition of cyclooxygenase-2 activity in human non-small cell lung cancer cells. Int J Oncol 2005;27:473-9.
El-Khoury V, Gomez D, Liautaud-Roger F, Trussardi-Régnier A, Dufer J. Effects of the histone deacetylase inhibitor trichostatin A on nuclear texture and c-jun gene expression in drug-sensitive and drug-resistant human H69 lung carcinoma cells. Cytometry A 2004;62:109-17.
Doi S, Soda H, Oka M, et al. The histone deacetylase inhibitor FR901228 induces caspase-dependent apoptosis via the mitochondrial pathway in small cell lung cancer cells. Mol Cancer Ther 2004;3:1397-402.
Witta SE, Gemmill RM, Hirsch FR, et al. Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res 2006;66:944-50.
Tsurutani J, Soda H, Oka M, et al. Antiproliferative effects of the histone deacetylase inhibitor FR901228 on small-cell lung cancer lines and drug-resistant sublines. Int J Cancer 2003;104:238-42.
Wang S, Yan-Neale Y, Fischer D, et al. Histone deacetylase 1 represses the small GTPase RhoB expression in human nonsmall lung carcinoma cell line. Oncogene 2003;22:6204-13.
Cao XX, Mohuiddin I, Ece F, McConkey DJ, Smythe WR. Histone deacetylase inhibitor downregulation of bcl-xl gene expression leads to apoptotic cell death in mesothelioma. Am J Respir Cell Mol Biol 2001;25:562-8.
Platta CS, Greenblatt DY, Kunnimalaiyaan M, Chen H. Valproic acid induces Notch1 signaling in small cell lung cancer cells. J Surg Res 2008;148:31-7.
Geng L, Cuneo KC, Fu A, Tu T, Atadja PW, Hallahan DE. Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasmin irradiated non-small cell lung cancer. Cancer Res 2006;66:11298-304.
Ruefli AA, Ausserlechner MJ, Bernhard D, et al. The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species. Proc Natl Acad Sci U S A 2001;98:10833-8.
Shao Y, Gao Z, Marks PA, Jiang X. Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc Natl Acad Sci U S A 2004;101:18030-5.
Magner WJ, Kazim AL, Stewart C, et al. Activation of MHC class I, II, and CD40 gene expression by histone deacetylase inhibitors. J Immunol 2000;165:7017-24.
Kato Y, Yoshimura K, Shin T, et al. Synergistic in vivo antitumor effect of the histone deacetylase inhibitor MS-275 in combination with interleukin 2 in a murine model of renal cell carcinoma. Clin Cancer Res 2007;13:4538-46.
Skov S, Pedersen MT, Andresen L, Straten PT, Woetmann A, Odum N. Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B. Cancer Res 2005;65:11136-45.
Reid T, Valone F, Lipera W, et al. Phase II trial of the histone deacetylase inhibitor pivaloyloxymethyl butyrate (Pivanex, AN-9) in advanced non-small cell lung cancer. Lung Cancer 2004;45:381-6. www.clinicaltrials.gov NCT00073385.
Schrump DS, Fischette MR, Nguyen DM, et al. Clinical and molecular responses in lung cancer patients receiving Romidepsin. Clin Cancer Res 2008;14:188-98.
Krug LM, Curley T, Schwartz L, et al. Potential role of histone deacetylase inhibitors in mesothelioma: clinical experience with suberoylanilide hydroxamic acid. Clin Lung Cancer 2006;7:257-61.
Kelly WK, O'Connor OA, Krug LM, et al. Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J Clin Oncol 2005;23:3923-31.
Edwards A, Li J, Atadja P, Bhalla K, Haura EB. Effect of the histone deacetylase inhibitor LBH589 against epidermal growth factor receptor-dependent human lung cancer cells. Mol Caner Ther 2007;6:2515-24.
Maiso P, Carvajal-Vergara X, Ocio EM, et al. The histone deacetylase inhibitor LBH589 is a potent antimyeloma agent that overcomes drug resistance. Cancer Res 2006;66:5781-9.
Ziegler A, Luedke GH, Fabbro D, Altmann KH, Stahel RA, Zanegemeister-Wittke U. Induction of apoptosis in small-cell lung cancer cells by an antisense oligonucleotide targeting the Bcl-2 coding sequence. J Natl Cancer Inst 1997;89:1027-36.
Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005;435:677-81.
Tse C, Shoemaker AR, Adickes J, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 2008;68:3421-8.
Rudin CM, Salgia R, Wang X, et al. Randomized phase II study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer: CALGB 30103. J Clin Oncol 2008;26:870-6.
Nakata S, Yoshida T, Horinaka M, Shiraishi T, Wakada M, Sakai T. Histone deacetylase inhibitors upregulate death receptor 5/TRAIL-R2 and sensitize apoptosis induced by TRAIL/APO2-L in human malignant tumor cells. Oncogene 2004;23:6261-71.
Guo F, Sigua C, Tao J, et al. Cotreatment with histone deacetylase inhibitor LAQ824 enhances Apo-2L/tumor necrosis factor-related apoptosis inducing ligand-induced death inducing signaling complex activity and apoptosis of human acute leukemia cells. Cancer Res 2004;64:2580-9.
Lundqvist A, Abrams SI, Schrump DS, et al. Bortezomib and depsipeptide sensitize tumors to tumor necrosis factor-related apoptosis-inducing ligand: a novel method to potentiate natural killer cell tumor cytotoxicity. Cancer Res 2006;66:7317-25.
Nencioni A, Beck J, Werth D, et al. Histone deacetylase inhibitors affect dendritic cell differentiation and immunogenicity. Clin Cancer Res 2007;13:3933-41.
Tao R, de Zoeten EF, Ozkaynak E, et al. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat Med 2007;13:1299-307.
Tanaka T, Delong P, Amin K, et al. Treatment of lung cancer using clinically relevant oral doses of the cyclooxygenase-2 inhibitor rofecoxib: potential value as adjuvant therapy after surgery. Ann Surg 2005;241:168-78.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.