title: The HDAC inhibitor Vorinostat diminishes the in vitro metastatic behavior of Osteosarcoma cells.
abstract: Osteosarcoma (OS) is the most common primary malignancy of bone and affects patients in the first two decades of life. The greatest determinant of survival is the presence of pulmonary metastatic disease. The role of epigenetic regulation in OS, specifically the biology of metastases, is unknown. Our previous study with the murine OS cell populations K7M2 and K12 demonstrated a significant correlation of metastatic potential with the DNA methylation level of tumor suppressor genes. In the current study, we investigated if the histone deacetylase (HDAC) inhibitor, vorinostat, could regulate the metastatic potential of highly metastatic OS cells. Our results revealed that vorinostat treatment of highly metastatic K7M2 OS cells was able to greatly reduce the proliferation and metastatic potential of the cells. Morphological features related to cell motility and invasion were changed by vorinostat treatment. In addition, the gene expressions of mTOR, ALDH1, and PGC-1 were downregulated by vorinostat treatment. These data suggest that vorinostat may be an effective modulator of OS cell metastatic potential and should be studied in preclinical models of metastatic OS.
authors.affiliation: Laboratory of Cancer Stem Cell, Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA 15217, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Mu
authors.affiliation: Laboratory of Cancer Stem Cell, Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA 15217, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brynien
authors.affiliation: Laboratory of Cancer Stem Cell, Stem Cell Research Center, University of Pittsburgh, Pittsburgh, PA 15217, USA.
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Weiss
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050697:Retinal Dehydrogenase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007527:Isoenzymes; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D000077337:Vorinostat; D000080924:Aldehyde Dehydrogenase 1 Family; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase