TY - JOUR T1 - A Dihydroxy-pentamethoxyflavone from <em>Gardenia obtusifolia</em> Suppresses Proliferation and Promotes Apoptosis of Tumor Cells Through Modulation of Multiple Cell Signaling Pathways JF - Anticancer Research JO - Anticancer Res SP - 3599 LP - 3610 VL - 30 IS - 9 AU - KANOKKARN PHROMNOI AU - SIMONE REUTER AU - BOKYUNG SUNG AU - PORNNGARM LIMTRAKUL AU - BHARAT B. AGGARWAL Y1 - 2010/09/01 UR - http://ar.iiarjournals.org/content/30/9/3599.abstract N2 - We sought to determine the molecular basis for the anticancer activities of 5,3′-dihydroxy-3,6,7,8,4′-pentamethoxyflavone (DH-PMF), isolated from Gardenia obtusifolia traditionally used in Thailand for a variety of ailments. As little as 1 μM DH-PMF inhibited the proliferation of prostate, colon, kidney, lung, head and neck, pancreas, breast, leukemia, and myeloma cancer cell lines. DH-PMF also suppressed the colony-forming ability of tumor cells, with 50% inhibition occurring at a dose less than 10 nM. DH-PMF induced G2/M and subG1 cell cycle arrest, increased the levels of p21WAF1/CIP1 and p27KIP1, and reduced the expression of cyclin D1, CDC2, and c-MYC. Furthermore, DH-PMF inhibited AKT and glycogen synthase kinase 3 beta (GSK3β) activation, reduced cell survival proteins, and induced apoptosis, as indicated by annexin V staining, TUNEL assay, and activation of caspase-8, -9 and -3. Overall, our results demonstrate that DH-PMF induces suppression of cell proliferation through modulation of AKT-GSK3β pathways and induction of cyclin-dependent kinase (CDK) inhibitors. ER -