SEARCH:   Advanced

Blood, 15 November 2007, Vol. 110, No. 10, pp. 3517-3525. Prepublished online as a Blood First Edition Paper on August 2, 2007; DOI 10.1182/blood-2007-03-079616. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-03-079616v1 110/10/3517    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pandey, M. K. Articles by Aggarwal, B. B. Search for Related Content PubMed PubMed Citation Articles by Pandey, M. K. Articles by Aggarwal, B. B. Related Collections Immunobiology Apoptosis Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS Gambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-B signaling pathway Manoj K. Pandey1, Bokyung Sung1, Kwang Seok Ahn1, Ajaikumar B. Kunnumakkara1, Madan M. Chaturvedi1, and Bharat B. Aggarwal1 1 Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX Gambogic acid (GA), a xanthone derived from the resin of the Garcinia hanburyi, has been recently demonstrated to bind transferrin receptor and exhibit potential anticancer effects through a signaling mechanism that is not fully understood. Because of the critical role of NF-B signaling pathway, we investigated the effects of GA on NF-B–mediated cellular responses and NF-B–regulated gene products in human leukemia cancer cells. Treatment of cells with GA enhanced apoptosis induced by tumor necrosis factor (TNF) and chemotherapeutic agents, inhibited the expression of gene products involved in antiapoptosis (IAP1 and IAP2, Bcl-2, Bcl-xL, and TRAF1), proliferation (cyclin D1 and c-Myc), invasion (COX-2 and MMP-9), and angiogenesis (VEGF), all of which are known to be regulated by NF-B. GA suppressed NF-B activation induced by various inflammatory agents and carcinogens and this, accompanied by the inhibition of TAK1/TAB1-mediated IKK activation, inhibited IB phosphorylation and degradation, suppressed p65 phosphorylation and nuclear translocation, and finally abrogated NF-B–dependent reporter gene expression. The NF-B activation induced by TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKKβ was also inhibited. The effect of GA mediated through transferrin receptor as down-regulation of the receptor by RNA interference reversed its effects on NF-B and apoptosis. Overall our results demonstrate that GA inhibits NF-B signaling pathway and potentiates apoptosis through its interaction with the transferrin receptor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. B. Aggarwal, M. E. Van Kuiken, L. H. Iyer, K. B. Harikumar, and B. Sung Molecular Targets of Nutraceuticals Derived from Dietary Spices: Potential Role in Suppression of Inflammation and Tumorigenesis Experimental Biology and Medicine, August 1, 2009; 234(8): 825 - 849. [Abstract] [Full Text] [PDF] R. E. Tiedemann, J. Schmidt, J. J. Keats, C.-X. Shi, Y. X. Zhu, S. E. Palmer, X. Mao, A. D. Schimmer, and A. K. Stewart Identification of a potent natural triterpenoid inhibitor of proteosome chymotrypsin-like activity and NF-{kappa}B with antimyeloma activity in vitro and in vivo Blood, April 23, 2009; 113(17): 4027 - 4037. [Abstract] [Full Text] [PDF] H. Gu, X. Wang, S. Rao, J. Wang, J. Zhao, F. L. Ren, R. Mu, Y. Yang, Q. Qi, W. Liu, et al. Gambogic acid mediates apoptosis as a p53 inducer through down-regulation of mdm2 in wild-type p53-expressing cancer cells Mol. Cancer Ther., October 1, 2008; 7(10): 3298 - 3305. [Abstract] [Full Text] [PDF] D. Zhai, C. Jin, C.-w. Shiau, S. Kitada, A. C. Satterthwait, and J. C. Reed Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins Mol. Cancer Ther., June 1, 2008; 7(6): 1639 - 1646. [Abstract] [Full Text] [PDF] T. Yi, Z. Yi, S.-G. Cho, J. Luo, M. K. Pandey, B. B. Aggarwal, and M. Liu Gambogic Acid Inhibits Angiogenesis and Prostate Tumor Growth by Suppressing Vascular Endothelial Growth Factor Receptor 2 Signaling Cancer Res., March 15, 2008; 68(6): 1843 - 1850. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020