Anticancer mechanisms of YC-1 in human lung cancer cell line, NCI-H226
Journal
Biochemical Pharmacology
Journal Volume
75
Journal Issue
2
Pages
360-368
Date Issued
2008
Author(s)
CHE-MING TENG
Abstract
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. ? 2007.
Subjects
Anti-metastasis; Apoptosis; Cell cycle arrest; NCI-H226; YC-1
SDGs
Other Subjects
1 benzyl 3 (5 hydroxymethyl 2 furyl)indazole; cyclin D1; cyclin dependent kinase 2; gelatinase A; gelatinase B; protein p16; protein p21; protein p53; protein tyrosine kinase; antineoplastic activity; apoptosis; article; cancer cell culture; cancer center; cancer growth; cancer inhibition; cell cycle G0 phase; cell cycle G1 phase; concentration (parameters); controlled study; cytotoxicity; drug exposure; drug screening; enzyme activity; human; human cell; lung cancer; metastasis; priority journal; protein blood level; upregulation; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Dose-Response Relationship, Drug; G1 Phase; Humans; Indazoles; Lung Neoplasms; Mitogen-Activated Protein Kinases; Neoplasm Metastasis
Type
journal article