SAHA, a HDAC inhibitor, has profound anti-growth activity against non-small cell lung cancer cells.
Current chemotherapy of advanced non-small cell lung cancer (NSCLC) produces only a modest increase in survival time. New approaches are needed for this disease. The development of lung cancer is associated with silencing tumor suppressor genes that can occur not only by deletion or mutation, but also by epigenetic changes including histone deacetylation of key lysines. Histone deacetylase inhibitor (HDACI) increases histone acetylation, resulting in DNA with a more open chromatin that favors transcription. We found that the HDACI, suberoylanilide hydroxamic acid (SAHA), suppressed cell growth of five non-small cell lung cancer cell lines in a dose-dependent manner (50% growth inhibition approximately 2 microM). Cell cycle assay by fluorescence-activated cell sorting (FACS) demonstrated that SAHA induced a significant G0-G1 growth arrest of NSCLC cells. Protein assay by Western blot analysis showed that SAHA induced expression of p21WAF1. These results demonstrated that administration of SAHA may be a novel approach to the treatment of non-small cell lung cancer.
Komatsu
Naoki
N
Department of Hematology/Respiratory, Cedars-Sinai Medical Center/University of California at Los Angeles School of Medicine, 90048, USA. komatuna@med.kochi-u.ac.jp
Kawamata
Norihiko
N
Takeuchi
Seisho
S
Yin
Dong
D
Chien
Wenwen
W
Miller
Carl W
CW
Koeffler
H Phillip
HP
D000107:Acetylation; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D000077337:Vorinostat
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D000077337:Vorinostat