@article {Phromnoi279, author = {Kanokkarn Phromnoi and Simone Reuter and Bokyung Sung and Sahdeo Prasad and Ramaswamy Kannappan and Vivek R. Yadav and Wisinee Chanmahasathien and Pornngarm Limtrakul and Bharat B. Aggarwal}, title = {RETRACTION: A Novel Pentamethoxyflavone Down-Regulates Tumor Cell Survival and Proliferative and Angiogenic Gene Products through Inhibition of IκB Kinase Activation and Sensitizes Tumor Cells to Apoptosis by Cytokines and Chemotherapeutic Agents}, volume = {79}, number = {2}, pages = {279--289}, year = {2011}, doi = {10.1124/mol.110.067512}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Most anticancer drugs have their origin in traditional medicinal plants. We describe here a flavone, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (PMF), from the leaves of the Thai plant Gardenia obtusifolia, that has anti-inflammatory and anticancer potential. Because the nuclear factor-κB (NF-κB) pathway is linked to inflammation and tumorigenesis, we investigated the effect of PMF on this pathway. We found that PMF suppressed NF-κB activation induced by inflammatory agents, tumor promoters, and carcinogens. This suppression was not specific to the cell type. Although PMF did not directly modify the ability of NF-κB proteins to bind to DNA, it inhibited IκBα (inhibitory subunit of NF-κB) kinase, leading to suppression of phosphorylation and degradation of IκBα, and suppressed consequent p65 nuclear translocation, thus abrogating NF-κB-dependent reporter gene expression. Suppression of the NF-κB cell signaling pathway by the flavone led to the inhibition of expression of NF-κB-regulated gene products that mediate inflammation (cyclooxygenase-2), survival (XIAP, survivin, Bcl-xL, and cFLIP), proliferation (cyclin D1), invasion (matrix metalloproteinase-9), and angiogenesis (vascular endothelial growth factor). Suppression of antiapoptotic gene products by PMF correlated with the enhancement of apoptosis induced by tumor necrosis factor-α and the chemotherapeutic agents cisplatin, paclitaxel, and 5-flurouracil. Overall, our results indicate that PMF suppresses the activation of NF-κB and NF-κB-regulated gene expression, leading to the enhancement of apoptosis. This is the first report to demonstrate that this novel flavone has anti-inflammatory and anticancer effects by targeting the IKK complex.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/79/2/279}, eprint = {https://molpharm.aspetjournals.org/content/79/2/279.full.pdf}, journal = {Molecular Pharmacology} }