Antitumor activity of suberoylanilide hydroxamic acid against human oral squamous cell carcinoma cell lines in vitro and in vivo
Autor: | Tatsuo Shirota, Tomohide Isobe, Tatsuhito Nagumo, Masashi Hatori, Tetsuhiko Tachikawa, Sayaka Takaoka, Sayaka Yoshiba, Masaru Ohashi, Satoru Shintani |
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Rok vydání: | 2009 |
Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cancer Research Pathology medicine.medical_specialty Cell Mice Nude Antineoplastic Agents Biology Hydroxamic Acids law.invention S Phase Mice Western blot law In vivo medicine Gene silencing Animals Humans Gene Vorinostat medicine.diagnostic_test business.industry G1 Phase Cell cycle In vitro stomatognathic diseases medicine.anatomical_structure Otorhinolaryngology Oncology Cell culture Carcinoma Squamous Cell Cancer research Suppressor Surgery Female Mouth Neoplasms Histone deacetylase Drug Screening Assays Antitumor Tumor Suppressor Protein p53 Oral Surgery business medicine.drug |
Zdroj: | Oral Oncology. 45:766-770 |
ISSN: | 1368-8375 |
DOI: | 10.1016/j.oraloncology.2008.11.009 |
Popis: | summary 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. |
Databáze: | OpenAIRE |
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