Antitumor activity of suberoylanilide hydroxamic acid against human oral squamous cell carcinoma cell lines in vitro and in vivo.
It has been reported recently that histone deacetylase inhibitors (HDACIs) can block the growth of a variety of malignant tumor cells by reversing the silencing of the tumor suppressor genes; these will be the anticancer agents of the next generation. In this study, we evaluated the antitumor effects of the HDACI suberoylanilide hydroxamic acid (SAHA) on oral squamous cell carcinoma (OSCC) and investigated its molecular mechanism. SAHA suppressed the in vitro proliferation of OSCC cell lines in a dose- and time-dependent manner. Flow cytometric analyses showed that treatment with SAHA led to G1 phase cell-cycle arrest of OSCC cells, accompanying a decrease in the percentage of S-phase cells. Western blot analyses demonstrated that the expression of p21 protein was remarkably augmented and hyperacetylation of p53 was induced after SAHA treatment. These results suggest that administration of SAHA suppresses OSCC growth through G1 phase arrest. Additionally, we observed that the growth of xenograft SAS tumors in nude mice was significantly blocked by the administration of SAHA without major adverse effects.
Nagumo
Tatsuhito
T
Department of Oral and Maxillofacial Surgery, Showa University, Kitasenzoku, Ohta-ku, Tokyo, Japan. tnagu@dent.showa-u.ac.jp
Takaoka
Sayaka
S
Yoshiba
Sayaka
S
Ohashi
Masaru
M
Shirota
Tatsuo
T
Hatori
Masashi
M
Isobe
Tomohide
T
Tachikawa
Tetsuhiko
T
Shintani
Satoru
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016196:S Phase / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000077337:Vorinostat
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006877:Hydroxamic Acids; D016159:Tumor Suppressor Protein p53; D000077337:Vorinostat