Main |
Browse Volumes |
Forthcoming Volumes |
Annals PrePrints |
Annals Extra |
E-mail Alerts |
Subscriptions & Orders |
New Proposals |
Author Guidelines |
About Annals |
Help |
 |
|
|
|
|
|
Part II. Transcriptional Control |
Targeting Signal-Transducer-and-Activator-of-Transcription-3 for Prevention and Therapy of CancerModern Target but Ancient Solution
BHARAT B. AGGARWALa,
GAUTAM SETHIa,
KWANG SEOK AHNa,
SANTOSH K. SANDURa,
MANOJ K. PANDEYa,
AJAIKUMAR B. KUNNUMAKKARAa,
BOKYUNG SUNGa AND
HARUYO ICHIKAWAa
a Department of Experimental Therapeutics, Cytokine Research Laboratory, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
Key Words: STAT3 • interleukin-6 • cancer • chemoresistance
Address for correspondence: Dr. Bharat B. Aggarwal, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Box 143, 1515 Holcombe Boulevard, Houston TX 77030. Voice: 713-794-1817; fax: 713-794-1613. e-mail: aggarwal{at}mdanderson.org
Recent evidence indicates a convergence of molecular targets for both prevention and therapy of cancer. Signal-transducer-and-activator-of-transcription-3 (STAT3), a member of a family of six different transcription factors, is closely linked with tumorigenesis. Its role in cancer is indicated by numerous avenues of evidence, including the following: STAT3 is constitutively active in tumor cells; STAT3 is activated by growth factors (e.g., EGF, TGF- , IL-6, hepatocyte growth factor) and oncogenic kinases (e.g., Src); STAT3 regulates the expression of genes that mediate proliferation (e.g., c-myc and cyclin D1), suppress apoptosis (e.g., Bcl-xL and survivin), or promote angiogenesis (e.g, VEGF); STAT3 activation has been linked with chemoresistance and radioresistance; and chemopreventive agents have been shown to suppress STAT3 activation. Thus inhibitors of STAT3 activation have potential for both prevention and therapy of cancer. Besides small peptides and oligonucleotides, numerous small molecules have been identified as blockers of STAT3 activation, including synthetic molecules (e.g., AG 490, decoy peptides, and oligonucleotides) and plant polyphenols (e.g., curcumin, resveratrol, flavopiridol, indirubin, magnolol, piceatannol, parthenolide, EGCG, and cucurbitacin). This article discusses these aspects of STAT3 in more detail.
This article has been cited by other articles:
|
|
|
|
 
K. S. Ahn, G. Sethi, B. Sung, A. Goel, R. Ralhan, and B. B. Aggarwal
Guggulsterone, a Farnesoid X Receptor Antagonist, Inhibits Constitutive and Inducible STAT3 Activation through Induction of a Protein Tyrosine Phosphatase SHP-1
Cancer Res.,
June 1, 2008;
68(11):
4406 - 4415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Umeda, S. Yano, K. Yamada, and H. Tachibana
Green Tea Polyphenol Epigallocatechin-3-gallate Signaling Pathway through 67-kDa Laminin Receptor
J. Biol. Chem.,
February 8, 2008;
283(6):
3050 - 3058.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Gatz and L. Wiesmuller
Take a break--resveratrol in action on DNA
Carcinogenesis,
February 1, 2008;
29(2):
321 - 332.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. E. Levy and C. A. Loomis
STAT3 Signaling and the Hyper-IgE Syndrome
N. Engl. J. Med.,
October 18, 2007;
357(16):
1655 - 1658.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K. Pathak, M. Bhutani, A. S. Nair, K. S. Ahn, A. Chakraborty, H. Kadara, S. Guha, G. Sethi, and B. B. Aggarwal
Ursolic Acid Inhibits STAT3 Activation Pathway Leading to Suppression of Proliferation and Chemosensitization of Human Multiple Myeloma Cells
Mol. Cancer Res.,
September 1, 2007;
5(9):
943 - 955.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
