title: UCN-01 (7-hydroxystaurosporine) induces apoptosis and G1 arrest of both primary and metastatic oral cancer cell lines in vitro.
abstract: OBJECTIVE
  Our aim was to clarify the in vitro antiproliferative effects of UCN-01 on human oral squamous cell carcinoma (OSCC) cell lines.
  
  
  METHODS
  Cell growth was measured by MTT assay, and cell cycling was assessed by flow cytometry. Changes in the levels of protein and protein phosphorylation were analyzed by Western blotting. In addition, tumor cell apoptosis was assessed by propidium iodide (PI) and annexin double-staining.
  
  
  RESULTS
  UCN-01 significantly inhibited the proliferation of all the OSCC cell lines, with a 50% inhibition concentration of about 300 nmol/L, and induced G1 arrest in these cell lines in a dose-dependent manner. Primary and metastatic oral cancer cell lines had different sensitivities to UCN-01. Our results showed that HSC-3 cells (primary-type OSCC) are less sensitive than LMF4 cells (metastatic-type OSCC) to UCN-01. In addition, the induction of p21 in OSCCs was found to be important for the suppression of tumor growth.
  
  
  CONCLUSIONS
  The results of this study suggest that UCN-01 induces apoptosis and G1 arrest in OSCCs, albeit with different sensitivity of the primary and metastatic cell lines to UCN-01.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Cervicognathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Otsubo
authors.forename: Ujjal Kumar
authors.initials: UK
authors.lastname: Bhawal
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nomura
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Mitani
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ozawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugiyama
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000473:pathology* / Q000556:secondary; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019311:Staurosporine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047428:Protein Kinase Inhibitors; C054852:7-hydroxystaurosporine; D011493:Protein Kinase C; D019311:Staurosporine