Abstract |
This study is the first to investigate isokotomolide A (IKA), a butanolide compound isolated from the leaves of Cinnamomum kotoense Kanehira & Sasaki (Lauraceaee), which exhibits an anti-proliferative activity in human non-small cell lung cancer A549 cells. The results show that IKA inhibits the proliferation of A549 by blocking cell cycle progression in the G0/G1 phase and inducing apoptosis. Blockade of cell cycle was associated with increased p21/WAF1 levels and reduced amounts of cyclin D1, cyclin E, Cdk2, Cdk4, and Cdk6 in a p53-mediated manner. IKA treatment also increased p53 phosphorylation (Ser15) and decreased the interaction of p53-MDM2. IKA treatment triggered the mitochondrial apoptotic pathway, indicated by changing Bax/Bcl-2 ratios, cytochrome c release and caspase-9 activation. In addition, pre-treatment of cells with caspase-9 inhibitor inhibited IKA-induced apoptosis, indicating that caspase-9 activation was involved in A549 cells' apoptosis induced by IKA. Our study reports here for the first time that the induction of p53/p21 and the initiation of the mitochondrial apoptotic system may participate in the anti-proliferative activity of IKA in human non-small cell lung cancer cells.
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Authors | Chung-Yi Chen, Ya-Ling Hsu, Yin-Yi Chen, Jen-Yu Hung, Ming-Shyan Huang, Po-Lin Kuo |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 574
Issue 2-3
Pg. 94-102
(Nov 28 2007)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 17707793
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- CDKN1A protein, human
- Cyclin-Dependent Kinase Inhibitor p21
- Tumor Suppressor Protein p53
- kotomolide A
- 4-Butyrolactone
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Topics |
- 4-Butyrolactone
(analogs & derivatives, pharmacology)
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, pathology)
- Cell Cycle
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cyclin-Dependent Kinase Inhibitor p21
(biosynthesis)
- Humans
- Lung Neoplasms
(drug therapy, pathology)
- Mitochondria
(drug effects)
- Tumor Suppressor Protein p53
(analysis, physiology)
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