Schools of Pharmacy, China Medical University, Taichung, Taiwan, ROC.
Anticancer Res. 2010 Oct;30(10):4187-92.
20-Fluoro-6,7-methylenedioxy-2-phenyl-4-quino-lone (CHM-1) has been reported to induce cell cycle arrest and apoptosis in many types of cancer cells. However, there is no available information to show CHM-1 affecting DNA damage and expression of associated repair genes. Herein, we investigated whether or not CHM-1 induced DNA damage and affected DNA repair gene expression in U-2 OS human osterogenic sarcoma cells. The comet assay showed that incubation of U-2 OS cells with 0, 0.75, 1.5, 3 and 6 μM of CHM-1 led to a longer DNA migration smear (comet tail). DNA gel electrophoresis showed that 3 μM of CHM-1 for 24 and 48 h treatment induced DNA fragmentation in U-2 OS cells. Real-time PCR analysis showed that treatment with 3 μM of CHM-1 for 24 h reduced the mRNA expression levels of ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR), breast cancer 1, early onset (BRCA1), 14-3-3sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK) and O(6)-methylguanine-DNA methyltransferase (MGMT) genes in a time-dependent manner. Taken together, the results indicate that CHM-1 caused DNA damage and reduced DNA repair genes in U-2 OS cells, which may be the mechanism for CHM-1-inhibited cell growth and induction of apoptosis.
20-氟-6,7-亚甲二氧基-2-苯基-4-喹诺酮（CHM-1）已被报道可诱导多种类型癌细胞的细胞周期停滞和凋亡。然而，尚无信息表明 CHM-1 影响 DNA 损伤和相关修复基因的表达。在此，我们研究了 CHM-1 是否在 U-2 OS 人成骨肉瘤细胞中诱导 DNA 损伤并影响 DNA 修复基因的表达。彗星试验表明，用 0、0.75、1.5、3 和 6 μM 的 CHM-1 孵育 U-2 OS 细胞会导致更长的 DNA 迁移斑点（彗星尾）。DNA 凝胶电泳显示，3 μM 的 CHM-1 处理 24 和 48 h 诱导 U-2 OS 细胞的 DNA 片段化。实时 PCR 分析显示，用 3 μM 的 CHM-1 处理 24 h 会降低 ATM、ATR、BRCA1、14-3-3σ、DNA-PK 和 MGMT 基因的 mRNA 表达水平。综上所述，结果表明 CHM-1 导致 U-2 OS 细胞的 DNA 损伤和降低 DNA 修复基因，这可能是 CHM-1 抑制细胞生长和诱导细胞凋亡的机制。
