Podchanart WanitchakoolSurawat JariyawatKanoknetr SuksenDarunee SoorukramPatoomratana TuchindaPawinee PiyachaturawatMahidol University2018-06-112018-06-112012-12-05European Journal of Pharmacology. Vol.696, No.1-3 (2012), 35-4218790712001429992-s2.0-84869081134https://repository.li.mahidol.ac.th/handle/123456789/15142Lung 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.Mahidol UniversityPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1016/j.ejphar.2012.09.029