Publication: Cleistanthoside A tetraacetate-induced DNA damage leading to cell cycle arrest and apoptosis with the involvement of p53 in lung cancer cells
Issued Date
2012-12-05
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ISSN
18790712
00142999
00142999
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2-s2.0-84869081134
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Mahidol University
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SCOPUS
Bibliographic Citation
European Journal of Pharmacology. Vol.696, No.1-3 (2012), 35-42
Suggested Citation
Podchanart Wanitchakool, Surawat Jariyawat, Kanoknetr Suksen, Darunee Soorukram, Patoomratana Tuchinda, Pawinee Piyachaturawat Cleistanthoside A tetraacetate-induced DNA damage leading to cell cycle arrest and apoptosis with the involvement of p53 in lung cancer cells. European Journal of Pharmacology. Vol.696, No.1-3 (2012), 35-42. doi:10.1016/j.ejphar.2012.09.029 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/15142
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Title
Cleistanthoside A tetraacetate-induced DNA damage leading to cell cycle arrest and apoptosis with the involvement of p53 in lung cancer cells
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Abstract
Lung cancer is the leading cause of cancer-related death worldwide and resistance to chemotherapeutic drugs is the major obstacle for effective treatment. The present study investigated the anticancer potential of cleistanthoside A tetraacetate (CAT), a derivative of cleistanthoside A from Phyllanthus taxodiifolius Beille on human lung cancer cells, LU-1. Multiple molecular approaches were used in this study and include measuring the anti-proliferative effect of CAT in LU-1 cells using flow cytometry; evaluating the induction of apoptosis by monitoring DNA fragmentation, phosphatidylserine externalization and activation of caspase-3 activity; and assaying the expression of regulatory proteins involved in cell cycle arrest and apoptosis using immunoblots. CAT potently inhibited LU-1 proliferation through an early G1 arrest with down-regulation of cdk4/6 and cyclin D1 proteins. CAT also inhibited DNA topoisomerase IIα activity resulting in DNA damage and increased the expression of the p53 protein with the subsequent induction of apoptosis. A decrease in the Bcl-2/Bax ratio, activation of caspase-3 activity and cleavage of PARP accompanied apoptosis. CAT is highly toxic to lung cancer and its primary targets are the inhibition of topoisomerase IIα activity and inducing apoptosis through a G1 arrest. These properties indicate that CAT is a promising anticancer agent for treatment of lung cancer. © 2012 Elsevier B.V.