Anticancer mechanisms of YC-1 in human lung cancer cell line, NCI-H226

作者：Chen Chun Jen; Hsu Mei Hua; Huang Li Jiau; Yamori Takao; Chung Fing Gung; Lee Fang Yu; Teng Che Ming; Kuo Sheng Chu^*

来源：Biochemical Pharmacology, 2008, 75(2): 360-368.

DOI：10.1016/j.bcp.2007.08.011

• YC-1
• NCI-H226
• cell cycle arrest
• apoptosis
• anti-metastasis

As part of a continuing search for potential anticancer drug candidates, 1-benzyl-3-(5-hydroxym ethyl-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 GO/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.

• 出版日期2008-1-15
• 单位河北医科大学; 中国医科大学