Radiosensitization of human tumor cells by phytochemicals

植物化学物质对人类肿瘤细胞的放射增敏作用

• 批准号: 23591845
• 负责人: NOBUO Kubota
• 金额: $ 3.41万
• 依托单位: Ibaraki Prefectural University of Health Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591845/
• 关键词: 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; Celastrol; がん幹細胞様細胞; celastrol; ヒト腫瘍細胞; ＤＮＡ修復

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.

我们研究了植物化学物质对人肿瘤细胞的放射敏化作用。异硫氰酸苄酯（BITC），一种常见的异硫氰酸酯之一，将人类肿瘤细胞敏感到辐射。 Celastrol是一种喹酮三萜，在p53野生和突变的Huma肺癌细胞中，也以类似方式增强了放射敏感性，表明该药物效应是p53-二依赖性的。 Celastrol通过破坏HSP90-CDC37复合物来抑制HSP90伴侣活性。因此，我们检查了PU-H71（一种嘌呤型HSP90抑制剂）PU-H71的放射敏活性。 PU-H71增强了人类肺癌细胞的放射敏感性，并明显抑制了DNA双链断裂的修复。接下来，我们研究了各种HSP90抑制剂对肝癌细胞中细胞杀死（HEPG2）和类似细胞（HEPG2-8960R）的癌细胞杀死的影响。 HEPG2-8960R细胞比HEPG2细胞对HSP90抑制剂更敏感。这些数据表明HSP90是癌的良好治疗靶标。