Anticancer mechanisms of YC-1 in human lung cancer cell line, NCI-H226.
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.
Chen
Chun-Jen
CJ
Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40421, Taiwan, ROC.
Hsu
Mei-Hua
MH
Huang
Li-Jiau
LJ
Yamori
Takao
T
Chung
Jing-Gung
JG
Lee
Fang-Yu
FY
Teng
Che-Ming
CM
Kuo
Sheng-Chu
SC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009362:Neoplasm Metastasis
D000970:Antineoplastic Agents; D007191:Indazoles; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D020928:Mitogen-Activated Protein Kinases