UCN-01 (7-hydroxystaurosporine) induces apoptosis and G1 arrest of both primary and metastatic oral cancer cell lines in vitro.
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.
Otsubo
Akira
A
Department of Oral and Maxillofacial Surgery, Division of Cervicognathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Bhawal
Ujjal Kumar
UK
Nomura
Yuji
Y
Mitani
Yoshitsugu
Y
Ozawa
Koichiro
K
Kuniyasu
Hiroki
H
Sugiyama
Masaru
M
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
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047428:Protein Kinase Inhibitors; C054852:7-hydroxystaurosporine; D011493:Protein Kinase C; D019311:Staurosporine