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Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma.

Fujita Y, Kato I, Iwai S, Ono K, Suzuki M, Sakurai Y, Ohnishi K, Ohnishi T, Yura Y - Radiat Oncol (2009)

Bottom Line: When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo compared with SAS/mp53 cells.The expression of p21 was induced in SAS/neo only, but G2 arrest-associated proteins including Wee1, cdc2, and cyclin B1 were altered in both cell lines.These results indicate that oral SCC cells with mutant-type are more resistant to BNCT than those with wild-type p53, and that the lack of G1 arrest and related apoptosis may contribute to the resistance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Osaka, Japan. fujisan@dent.osaka-u.ac.jp

ABSTRACT

Background: Boron neutron capture therapy (BNCT) is a selective radiotherapy, being effective for the treatment of even advanced malignancies in head and neck regions as well as brain tumors and skin melanomas. To clarify the role of p53 gene, the effect of BNCT on oral squamous cell carcinoma (SCC) cells showing either wild- (SAS/neo) or mutant-type (SAS/mp53) p53 was examined.

Methods: Cells were exposed to neutron beams in the presence of boronophenylalanine (BPA) at Kyoto University Research Reactor. Treated cells were monitored for modulations in colony formation, proliferation, cell cycle, and expression of cell cycle-associated proteins.

Results: When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo compared with SAS/mp53 cells. Cell cycle arrest at the G1 checkpoint was observed in SAS/neo, but not in SAS/mp53. Apoptotic cells increased from 6 h after BNCT in SAS/neo and 48 h in SAS/mp53 cells. The expression of p21 was induced in SAS/neo only, but G2 arrest-associated proteins including Wee1, cdc2, and cyclin B1 were altered in both cell lines.

Conclusion: These results indicate that oral SCC cells with mutant-type are more resistant to BNCT than those with wild-type p53, and that the lack of G1 arrest and related apoptosis may contribute to the resistance. At a physical dose affecting the cell cycle, BNCT inhibits oral SCC cells in p53-dependent and -independent manners.

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Related in: MedlinePlus

Induction of cell cycle arrest by BNCT. A. SAS/neo and SAS/mp53 cells were treated with BNCT and then subjected to flow cytometric analysis. B. Based on an analysis of DNA histograms, the percentages of cells in sub-G1, G0/G1, S, and G2/M phases were evaluated.
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Figure 3: Induction of cell cycle arrest by BNCT. A. SAS/neo and SAS/mp53 cells were treated with BNCT and then subjected to flow cytometric analysis. B. Based on an analysis of DNA histograms, the percentages of cells in sub-G1, G0/G1, S, and G2/M phases were evaluated.

Mentions: SAS/neo cells were treated with BNCT at a dose of 6 Gy and then subjected to flow cytometric analysis. Initially, the rate of SAS/neo cells in the G0/G1 phase was 30%, and it increased to 39% at 6 h after BNCT. At 12 h, it decreased to 6%, and cells in the G2/M phase were increased to 34%. Sub-G1 peaks, indicating apoptotic cells, appeared from 6 h after BNCT (Figure 3). In SAS/mp53 cells, however, there was no increase of G0/G1 phase cells at 6 h after BNCT; rather, they decreased slightly (Figure 3). At 12 h after BNCT, the proportion of cells in the G2/M phase was increased to 40%, indicating arrest at the G2/M checkpoint. A small sub-G1 population appeared at 48 h after BNCT.


Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma.

Fujita Y, Kato I, Iwai S, Ono K, Suzuki M, Sakurai Y, Ohnishi K, Ohnishi T, Yura Y - Radiat Oncol (2009)

Induction of cell cycle arrest by BNCT. A. SAS/neo and SAS/mp53 cells were treated with BNCT and then subjected to flow cytometric analysis. B. Based on an analysis of DNA histograms, the percentages of cells in sub-G1, G0/G1, S, and G2/M phases were evaluated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803486&req=5

Figure 3: Induction of cell cycle arrest by BNCT. A. SAS/neo and SAS/mp53 cells were treated with BNCT and then subjected to flow cytometric analysis. B. Based on an analysis of DNA histograms, the percentages of cells in sub-G1, G0/G1, S, and G2/M phases were evaluated.
Mentions: SAS/neo cells were treated with BNCT at a dose of 6 Gy and then subjected to flow cytometric analysis. Initially, the rate of SAS/neo cells in the G0/G1 phase was 30%, and it increased to 39% at 6 h after BNCT. At 12 h, it decreased to 6%, and cells in the G2/M phase were increased to 34%. Sub-G1 peaks, indicating apoptotic cells, appeared from 6 h after BNCT (Figure 3). In SAS/mp53 cells, however, there was no increase of G0/G1 phase cells at 6 h after BNCT; rather, they decreased slightly (Figure 3). At 12 h after BNCT, the proportion of cells in the G2/M phase was increased to 40%, indicating arrest at the G2/M checkpoint. A small sub-G1 population appeared at 48 h after BNCT.

Bottom Line: When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo compared with SAS/mp53 cells.The expression of p21 was induced in SAS/neo only, but G2 arrest-associated proteins including Wee1, cdc2, and cyclin B1 were altered in both cell lines.These results indicate that oral SCC cells with mutant-type are more resistant to BNCT than those with wild-type p53, and that the lack of G1 arrest and related apoptosis may contribute to the resistance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Osaka, Japan. fujisan@dent.osaka-u.ac.jp

ABSTRACT

Background: Boron neutron capture therapy (BNCT) is a selective radiotherapy, being effective for the treatment of even advanced malignancies in head and neck regions as well as brain tumors and skin melanomas. To clarify the role of p53 gene, the effect of BNCT on oral squamous cell carcinoma (SCC) cells showing either wild- (SAS/neo) or mutant-type (SAS/mp53) p53 was examined.

Methods: Cells were exposed to neutron beams in the presence of boronophenylalanine (BPA) at Kyoto University Research Reactor. Treated cells were monitored for modulations in colony formation, proliferation, cell cycle, and expression of cell cycle-associated proteins.

Results: When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo compared with SAS/mp53 cells. Cell cycle arrest at the G1 checkpoint was observed in SAS/neo, but not in SAS/mp53. Apoptotic cells increased from 6 h after BNCT in SAS/neo and 48 h in SAS/mp53 cells. The expression of p21 was induced in SAS/neo only, but G2 arrest-associated proteins including Wee1, cdc2, and cyclin B1 were altered in both cell lines.

Conclusion: These results indicate that oral SCC cells with mutant-type are more resistant to BNCT than those with wild-type p53, and that the lack of G1 arrest and related apoptosis may contribute to the resistance. At a physical dose affecting the cell cycle, BNCT inhibits oral SCC cells in p53-dependent and -independent manners.

Show MeSH
Related in: MedlinePlus