2013 Fiscal Year Final Research Report
Radiosensitization of human tumor cells by phytochemicals
| Project/Area Number |
23591845
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Ibaraki Prefectural University of Health Science |
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Principal Investigator |
NOBUO Kubota 茨城県立医療大学, 保健医療学部, 教授 (20046139)
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| Research Collaborator |
OHNISHI Ken 茨城県立医療大学, 保健医療学部, 教授 (50152195)
FUJII Yoshihro 茨城県立医療大学, 保健医療学部, 助教 (20637540)
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| Project Period (FY) |
2011 – 2013
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| Keywords | フィトケミカル / ベンチルイソチオシアネート / セラストロール / 放射線増感 / アポトーシス / DNA二本鎖切断修復 / Hsp90阻害剤 |
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| Research Abstract |
We studied radiosensitizing effects of phytochemicals on human tumor cells. Benzyl isothiocyanate (BITC), one of the common dietary isothiocyanates, sensitized human tumor cells to radiation. Celastrol, a quinone methide triterpene, also enhanced radiosensitivity in a similar fashion in both p53 wild and mutated huma lung cancer cells, indicating that the drug effect is p53-ondependent. Celastrol inhibits Hsp90 chaperone activity by disrupting Hsp90-Cdc37 complex. Thus, we examined the radiosensitizing activity of PU-H71, a purine-scaffold Hsp90 inhibitor. PU-H71 enhanced radiosensitivity of human lung cancer cells and markedly inhibited the repair of DNA double strand breaks. Next, we studied the effect of various Hsp90 inhibitors on cell killing in hepatoma cancer cells (HepG2) and cancer stem like cells (HepG2-8960R). HepG2-8960R cells are far more sensitive to Hsp90 inhibitors than HepG2 cells. These data indicate that Hsp90 is good therapeutic target for carcinoma.
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