A Dihydroxy-pentamethoxyflavone from Gardenia obtusifolia Suppresses Proliferation and Promotes Apoptosis of Tumor Cells Through Modulation of Multiple Cell Signaling Pathways

作者：Phromnoi Kanokkarn; Reuter Simone; Sung Bokyung; Limtrakul Pornngarm^*; Aggarwal Bharat B

来源：Anticancer Research, 2010, 30(9): 3599-3610.

• AKT
• GSK3beta
• natural products
• plant extract
• CDK inhibitor

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 mu M 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 G(2)/M and subG(1) cell cycle arrest, increased the levels of p21(WAF1/CIP1) and p27(KIP1) and reduced the expression of cyclin D1, CDC2, and c-MYC. Furthermore, DH-PMF inhibited AKT and glycogen synthase kinase 3 beta (GSK3 beta) 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-GSK3 beta pathways and induction of cyclin-dependent kinase (CDK) inhibitors.

• 出版日期2010-9