Effect of neutron capture therapy on the cell cycle of human squamous cell carcinoma cells.
OBJECTIVE
The effects of boronophenylalanine (BPA)-mediated boron neutron capture therapy (BNCT) on the growth potential and cell cycle of human oral squamous cell carcinoma (SCC) cells were examined.


METHODS
SAS cells expressing a functional wild-type p53 were exposed to neutron beams in the presence of BPA and growth potential was measured by colony formation assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell cycle and cell cycle-related proteins were examined by flow cytometry and immunoblot analysis.


RESULTS
BNCT affected the colony-forming ability and viability of SAS cells. In the flow-cytometric analysis of BNCT-treated cells, the cell cycle was arrested at the G1 and G2 checkpoints, and sub-G1 cells appeared. Apoptotic cells were detected by nuclear DNA staining. Immunoblot analysis revealed the phosphorylation of p53, up-regulation of p21, and down-regulation of retinoblastoma (Rb) gene protein at 6 h after BNCT. Twelve hours after BNCT, the up-regulation of Wee1, phosphorylation of cdc2, and up-regulation of cyclin B1 were observed. Cleavage of poly (ADP-ribose) polymerase (PARP) occurred from 6 h after BNCT.


CONCLUSIONS
These results indicate that the early inhibitory effect of BNCT on the growth of human oral SCC cells can be ascribed to arrest at the G1 and G2 checkpoints and apoptosis associated with G1 arrest.
Kamida
Akitoshi
A
Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Osaka, Japan.
Fujita
Yusei
Y
Kato
Itsuro
I
Iwai
Soichi
S
Ono
Koji
K
Suzuki
Minoru
M
Sakurai
Yoshinori
Y
Yura
Yoshiaki
Y
D001896:Boron Compounds / Q000494:pharmacology; D016754:Boron Neutron Capture Therapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D001896:Boron Compounds; D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53; D010649:Phenylalanine; C033685:4-boronophenylalanine