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Isokotomolide A, a new butanolide extracted from the leaves of Cinnamomum kotoense, arrests cell cycle progression and induces apoptosis through the induction of p53/p21 and the initiation of mitochondrial system in human non-small cell lung cancer A549 cells.
Eur J Pharmacol. 2007 Nov 28; 574(2-3):94-102.EJ

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.

Authors+Show Affiliations

Basic Medical Science Education Center, Fooyin University, Kaohsiung, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17707793

Citation

Chen, Chung-Yi, et al. "Isokotomolide A, a New Butanolide Extracted From the Leaves of Cinnamomum Kotoense, Arrests Cell Cycle Progression and Induces Apoptosis Through the Induction of P53/p21 and the Initiation of Mitochondrial System in Human Non-small Cell Lung Cancer A549 Cells." European Journal of Pharmacology, vol. 574, no. 2-3, 2007, pp. 94-102.
Chen CY, Hsu YL, Chen YY, et al. Isokotomolide A, a new butanolide extracted from the leaves of Cinnamomum kotoense, arrests cell cycle progression and induces apoptosis through the induction of p53/p21 and the initiation of mitochondrial system in human non-small cell lung cancer A549 cells. Eur J Pharmacol. 2007;574(2-3):94-102.
Chen, C. Y., Hsu, Y. L., Chen, Y. Y., Hung, J. Y., Huang, M. S., & Kuo, P. L. (2007). Isokotomolide A, a new butanolide extracted from the leaves of Cinnamomum kotoense, arrests cell cycle progression and induces apoptosis through the induction of p53/p21 and the initiation of mitochondrial system in human non-small cell lung cancer A549 cells. European Journal of Pharmacology, 574(2-3), 94-102.
Chen CY, et al. Isokotomolide A, a New Butanolide Extracted From the Leaves of Cinnamomum Kotoense, Arrests Cell Cycle Progression and Induces Apoptosis Through the Induction of P53/p21 and the Initiation of Mitochondrial System in Human Non-small Cell Lung Cancer A549 Cells. Eur J Pharmacol. 2007 Nov 28;574(2-3):94-102. PubMed PMID: 17707793.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isokotomolide A, a new butanolide extracted from the leaves of Cinnamomum kotoense, arrests cell cycle progression and induces apoptosis through the induction of p53/p21 and the initiation of mitochondrial system in human non-small cell lung cancer A549 cells. AU - Chen,Chung-Yi, AU - Hsu,Ya-Ling, AU - Chen,Yin-Yi, AU - Hung,Jen-Yu, AU - Huang,Ming-Shyan, AU - Kuo,Po-Lin, Y1 - 2007/07/24/ PY - 2007/03/02/received PY - 2007/07/07/revised PY - 2007/07/16/accepted PY - 2007/8/21/pubmed PY - 2008/1/18/medline PY - 2007/8/21/entrez SP - 94 EP - 102 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 574 IS - 2-3 N2 - 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17707793/Isokotomolide_A_a_new_butanolide_extracted_from_the_leaves_of_Cinnamomum_kotoense_arrests_cell_cycle_progression_and_induces_apoptosis_through_the_induction_of_p53/p21_and_the_initiation_of_mitochondrial_system_in_human_non_small_cell_lung_cancer_A549_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00801-1 DB - PRIME DP - Unbound Medicine ER -