![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
-Dependent and -Independent Pathways
Department of Biochemistry and Biophysics (S.C., S.P., S.S.) and Department of Veterinary Physiology and Pharmacology (S.S.), Texas A&M University, College Station, Texas; Department of Blood and Marrow Transplantation, Section of Molecular Hematology and Therapy, University of Texas, M.D. Anderson Cancer Center, Houston, Texas (M.K., M.A., I.S.); and Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas (S.S.)
2-Cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) and the corresponding methyl (CDDO-Me) and imidazole (CDDO-Im) esters induce peroxisome proliferator-activated receptor 
(PPAR)-dependent transactivation in SW-480 colon cancer cells, and these responses were inhibited by small inhibitory RNA for PPAR. Moreover, in a mammalian two-hybrid assay using the PPAR2-VP16 fusion plasmid and GAL4-coactivator/corepressor chimeras and a construct (pGAL4) containing five tandem GAL4 response elements, CDDO, CDDO-Me, and CDDO-IM induce transactivation and PPAR interaction with multiple coactivators. A major difference among the three PPAR agonists was the higher activity of CDDO-Im to induce PPAR interactions with the corepressor SMRT. CDDO, CDDO-Me, and CDDO-Im inhibited SW-480, HCT-116, and HT-29 colon cancer cell proliferation at low concentrations and induced cell death at higher concentrations. Growth inhibition at lower concentrations correlated with induction of the tumor suppressor gene caveolin-1 which is known to inhibit colon cancer cell growth. Induction of caveolin-1 by CDDO, CDDO-Me, and CDDO-Im was inhibited by the PPAR antagonist N-(4'-aminopyridyl-2-chloro-5-nitrobenzamide (T007), whereas higher doses induced apoptosis [poly(ADP-ribose) polymerase cleavage], which was not inhibited by T007. These results illustrate that CDDO-, CDDO-Me, and CDDO-Im induce both PPAR-dependent and -independent responses in colon cancer cells, and activation of these pathways are separable and concentration-dependent for all three compounds.
Received for publication January 24, 2005.
Accepted for publication March 18, 2005.
Address correspondence to: Dr. Stephen Safe, Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466. E-mail: ssafe{at}cvm.tamu.edu
This article has been cited by other articles:
|
|
 |
|
  H. E. Ferguson, T. H. Thatcher, K. C. Olsen, T. M. Garcia-Bates, C. J. Baglole, R. M. Kottmann, E. R. Strong, R. P. Phipps, and P. J. Sime Peroxisome proliferator-activated receptor-{gamma} ligands induce heme oxygenase-1 in lung fibroblasts by a PPAR{gamma}-independent, glutathione-dependent mechanism Am J Physiol Lung Cell Mol Physiol, November 1, 2009; 297(5): L912 - L919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lei, M. Abdelrahim, S. D. Cho, S. Liu, S. Chintharlapalli, and S. Safe 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit colon cancer cell and tumor growth through activation of c-jun N-terminal kinase Carcinogenesis, June 1, 2008; 29(6): 1139 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Papineni, S. Chintharlapalli, and S. Safe Methyl 2-Cyano-3,11-dioxo-18{beta}-olean-1,12-dien-30-oate Is a Peroxisome Proliferator-Activated Receptor-{gamma} Agonist That Induces Receptor-Independent Apoptosis in LNCaP Prostate Cancer Cells Mol. Pharmacol., February 1, 2008; 73(2): 553 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. York, M. Abdelrahim, S. Chintharlapalli, S. D. Lucero, and S. Safe 1,1-Bis(3'-Indolyl)-1-(p-Substitutedphenyl)methanes Induce Apoptosis and Inhibit Renal Cell Carcinoma Growth Clin. Cancer Res., November 15, 2007; 13(22): 6743 - 6752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Koschmieder, F. D'Alo, H. Radomska, C. Schoneich, J. S. Chang, M. Konopleva, S. Kobayashi, E. Levantini, N. Suh, A. Di Ruscio, et al. CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer binding protein alpha Blood, November 15, 2007; 110(10): 3695 - 3705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chintharlapalli, S. Papineni, S. Liu, I. Jutooru, G. Chadalapaka, S.-d. Cho, R. S. Murthy, Y. You, and S. Safe 2-Cyano-lup-1-en-3-oxo-20-oic acid, a cyano derivative of betulinic acid, activates peroxisome proliferator-activated receptor {gamma} in colon and pancreatic cancer cells Carcinogenesis, November 1, 2007; 28(11): 2337 - 2346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Ling, M. Konopleva, Z. Zeng, V. Ruvolo, L. C. Stephens, W. Schober, T. McQueen, M. Dietrich, T. L. Madden, and M. Andreeff The Novel Triterpenoid C-28 Methyl Ester of 2-Cyano-3, 12-Dioxoolen-1, 9-Dien-28-Oic Acid Inhibits Metastatic Murine Breast Tumor Growth through Inactivation of STAT3 Signaling Cancer Res., May 1, 2007; 67(9): 4210 - 4218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chintharlapalli, S. Papineni, I. Jutooru, A. McAlees, and S. Safe Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator-activated receptor {gamma} agonists in colon cancer cells Mol. Cancer Ther., May 1, 2007; 6(5): 1588 - 1598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chintharlapalli, S. Papineni, S. K. Ramaiah, and S. Safe Betulinic Acid Inhibits Prostate Cancer Growth through Inhibition of Specificity Protein Transcription Factors Cancer Res., March 15, 2007; 67(6): 2816 - 2823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chintharlapalli, S. Papineni, and S. Safe 1,1-Bis(3'-Indolyl)-1-(p-substitutedphenyl)methanes Inhibit Growth, Induce Apoptosis, and Decrease the Androgen Receptor in LNCaP Prostate Cancer Cells through Peroxisome Proliferator-Activated Receptor {gamma}-Independent Pathways Mol. Pharmacol., February 1, 2007; 71(2): 558 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Yore, K. T. Liby, T. Honda, G. W. Gribble, and M. B. Sporn The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole blocks nuclear factor-{kappa}B activation through direct inhibition of I{kappa}B kinase {beta} Mol. Cancer Ther., December 1, 2006; 5(12): 3232 - 3239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Schlezinger, J. K. Emberley, and D. H. Sherr Activation of Multiple Mitogen-Activated Protein Kinases in Pro/Pre-B Cells by GW7845, a Peroxisome Proliferator-Activated Receptor {gamma} Agonist, and Their Contribution to GW7845-Induced Apoptosis Toxicol. Sci., August 1, 2006; 92(2): 433 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Liby, N. Voong, C. R. Williams, R. Risingsong, D. B. Royce, T. Honda, G. W. Gribble, M. B. Sporn, and J. J. Letterio The Synthetic Triterpenoid CDDO-Imidazolide Suppresses STAT Phosphorylation and Induces Apoptosis in Myeloma and Lung Cancer Cells. Clin. Cancer Res., July 15, 2006; 12(14): 4288 - 4293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chintharlapalli, S. Papineni, and S. Safe 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit colon cancer cell and tumor growth through PPAR{gamma}-dependent and PPAR{gamma}-independent pathways Mol. Cancer Ther., May 1, 2006; 5(5): 1362 - 1370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Samudio, M. Konopleva, H. Pelicano, P. Huang, O. Frolova, W. Bornmann, Y. Ying, R. Evans, R. Contractor, and M. Andreeff A Novel Mechanism of Action of Methyl-2-cyano-3,12 Dioxoolean-1,9 Diene-28-oate: Direct Permeabilization of the Inner Mitochondrial Membrane to Inhibit Electron Transport and Induce Apoptosis Mol. Pharmacol., April 1, 2006; 69(4): 1182 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Shishodia, G. Sethi, M. Konopleva, M. Andreeff, and B. B. Aggarwal A Synthetic Triterpenoid, CDDO-Me, Inhibits I{kappa}B{alpha} Kinase and Enhances Apoptosis Induced by TNF and Chemotherapeutic Agents through Down-Regulation of Expression of Nuclear Factor {kappa}B-Regulated Gene Products in Human Leukemic Cells Clin. Cancer Res., March 15, 2006; 12(6): 1828 - 1838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Konopleva, W. Zhang, Y.-X. Shi, T. McQueen, T. Tsao, M. Abdelrahim, M. F. Munsell, M. Johansen, D. Yu, T. Madden, et al. Synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest in HER2-overexpressing breast cancer cells. Mol. Cancer Ther., February 1, 2006; 5(2): 317 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Kassouf, S. Chintharlapalli, M. Abdelrahim, G. Nelkin, S. Safe, and A. M. Kamat Inhibition of Bladder Tumor Growth by 1,1-Bis(3'-Indolyl)-1-(p-Substitutedphenyl)Methanes: A New Class of Peroxisome Proliferator-Activated Receptor {gamma} Agonists Cancer Res., January 1, 2006; 66(1): 412 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chintharlapalli, S. Papineni, S. J. Baek, S. Liu, and S. Safe 1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes Are Peroxisome Proliferator-Activated Receptor {gamma} Agonists but Decrease HCT-116 Colon Cancer Cell Survival through Receptor-Independent Activation of Early Growth Response-1 and Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Mol. Pharmacol., December 1, 2005; 68(6): 1782 - 1792. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
