GL3, a Novel 4β-Anilino-4'-O-Demethyl-4-Desoxypodophyllotoxin Analog, Traps Topoisomerase II Cleavage Complexes and Exerts Anticancer Activities.

ABSTRACT: A novel VP-16 derivative, 4β-[N -(4‴-acetyloxyl-phenyl-1‴-carbonyl)-4″-aminoanilino]-4'-O-demethyl-4-desoxypodophyllotoxin (GL3), displayed a wide range of cytotoxicity in a panel of human tumor cell lines, with half-maximal inhibitory concentration (IC(50)) values ranging from 0.82 to 4.88 µM, much less than that of VP-16 (4.18-39.43 µM). Importantly, GL3 induces more significant apoptosis and cell cycle arrest than VP-16. The molecular and cellular machinery studies showed that GL3 functions as a topoisomerase II (Top 2) poison through direct binding to the enzyme, and the advanced cell-killing activities of GL3 were ascribed to its potent effects on trapping Top 2-DNA cleavage complex, Moreover, GL3-triggered DNA double-strand breaks and apoptotic cell death were in a Top 2-dependent ma

SUBMITTER: Yang XC 

PROVIDER: S-EPMC3573656 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature