Sodium Salicylate(NaSaL) Induces Apoptosis of NCI-H1299 Lung Carcinoma Cells via Activation Caspase-3 Protease.
10.4046/trd.2002.53.5.485
- Author:
Hyeok SHIM
1
;
Sei Hoon YANG
;
Sang Myeon BAK
;
Eun Taik JEONG
Author Information
1. Department of Internal Medicine, College of Medicine, Wonkwang University, Iksan, Korea. yshpul@wonkwang.ac.kr
- Publication Type:Original Article
- Keywords:
NCI-H1299;
NaSaL;
Apoptosis;
Caspase-3 protease
- MeSH:
Humans;
Lung Neoplasms
- From:Tuberculosis and Respiratory Diseases
2002;53(5):485-496
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful in the chemoprevention of colon cancers. Continuous NSAID use results in a 40% to 50% reduction in the relative risk of colorectal cancer. The precise mechanism by which NSAIDs prevent and /or cause the regression of colorectal tumors is not known. Some investigators have reported that certain NSAIDs induce apoptosis and alter the expression of the cell cycle regulatory genes in some carcinoma cells when administered at a relatively high concentration. However, the possibility of NSAIDs application as chemopreventive agents in lung cancers remains to be elucidated. To address this question, the human lung cancer cell line NCI-H1299 was used to investigate whether or not NSAIDs might induce the apoptotic death of NCI-H1299 cells. METHOD: A viability test was carried out using a MTT assay. Apoptosis was measured by flow cytometric analysis and nuclear staining(DAPI). The catalytic activity of the caspase family was measured by the fluorogenic cleavage of biosubstrates. To define the mechanical basis of apoptosis, western blot was performed to analyze the expression of the cleavage of the death substrates(PARP and ICAD). RESULTS: NaSaL significantly decreased the viability of the NCI-H1299 cells, which was revealed as apoptosis characterized by an increase in the subG0/G1 population and nuclear fragmentation. The catalytic activity of caspase-3 protease began to increase after 24 Hr and reached a peak 30 Hr after treatment with 10 mM NaSaL. In contrast, caspase-6, 8, and 9 proteases did not have a significantly altered enzymatic activity. Consistent with activation of caspase-3 protease, NaSaL induced the cleavage of the protease biosubstrate. CONCLUSION: NaSaL induces the apoptotic death of NCI-H1299 human lung cancer cells via the activation of caspase-3 protease.
