Chen Chun-Jen, Hsu Mei-Hua, Huang Li-Jiau, Yamori Takao, Chung Jing-Gung, Lee Fang-Yu, Teng Che-Ming, Kuo Sheng-Chu
Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40421, Taiwan, ROC.
Biochem Pharmacol. 2008 Jan 15;75(2):360-8. doi: 10.1016/j.bcp.2007.08.011. Epub 2007 Aug 17.
As part of a continuing search for potential anticancer drug candidates, 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) was evaluated in the Japanese Cancer Institute's (JCI) in vitro disease-oriented anticancer screen. The results indicated that YC-1 showed impressive selective toxicity against the NCI-H226 cell line. Therefore, the molecular mechanism by which YC-1 affects NCI-H226 cell growth was studied. YC-1 inhibited NCI-H226 cell growth in a time- and a concentration-dependent manner. YC-1 suppressed the protein levels of cyclin D1, CDK2 and cdc25A, up-regulated p16, p21 and p53, increased the number of NCI-H226 cells in the G0/G1 phase of the cell cycle. Long exposure to YC-1 induced apoptosis by mitochondrial-dependent pathway. In addition, YC-1 inhibited MMP-2 and MMP-9 protein activities to abolish tumor cells metastasis. These findings suggest a mechanism of cytotoxic action of YC-1 and indicate that YC-1 may be a promising chemotherapy agent against lung cancer.
作为持续寻找潜在抗癌药物候选物的一部分，1-苄基-3-(5-羟甲基-2-呋喃基)吲唑(YC-1)在日本癌症研究所(JCI)以疾病为导向的体外抗癌筛选中进行了评估。结果表明，YC-1对NCI-H226细胞系表现出令人印象深刻的选择性毒性。因此，研究了YC-1影响NCI-H226细胞生长的分子机制。YC-1以时间和浓度依赖性方式抑制NCI-H226细胞生长。YC-1抑制细胞周期蛋白D1、CDK2和cdc25A的蛋白水平，上调p16、p21和p53，增加处于细胞周期G0/G1期的NCI-H226细胞数量。长时间暴露于YC-1通过线粒体依赖性途径诱导细胞凋亡。此外，YC-1抑制MMP-2和MMP-9蛋白活性以消除肿瘤细胞转移。这些发现提示了YC-1的细胞毒性作用机制，并表明YC-1可能是一种有前途的抗肺癌化疗药物。
