Skip Navigation


Carcinogenesis Advance Access originally published online on December 6, 2005
Carcinogenesis 2006 27(4):717-728; doi:10.1093/carcin/bgi270
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
27/4/717    most recent
bgi270v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (49)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Abdelrahim, M.
Right arrow Articles by Safe, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Abdelrahim, M.
Right arrow Articles by Safe, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

3,3'-Diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5

Maen Abdelrahim 1, Kristen Newman 1, Kathy Vanderlaag 2, Ismael Samudio 3 and Stephen Safe 1, 2, *

1 Institute of Biosciences and Technology, The Texas A&M University System Health Science Center, 2121 W. Holcombe Boulevard, Houston, TX 77030, USA, 2 Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA and 3 Department of Blood and Marrow Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA

* To whom correspondence should be addressed at: Department of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, College Station, TX 77843-4466, USA. Tel: +1 979 845 5988; Fax: +1 979 862 4929; Email: ssafe{at}cvm.tamu.edu

3,3'-Diindolylmethane (DIM), ring-substituted DIMs and 1,1-bis(3'-indolyl)-1-(p-substitutedphenyl)methanes (C-DIMs) inhibit growth of Panc-1 and Panc-28 pancreatic cancer cells. Although DIMs (diarylmethanes) and selected C-DIMs (triarylmethanes), such as the p-t-butyl derivative (DIM-C-pPhtBu), activate the aryl hydrocarbon receptor and peroxisome proliferator-activated receptor {gamma}, respectively, this study shows that both DIM and DIM-C-pPhtBu induce common receptor-independent pathways. Both DIM and DIM-C-pPhtBu increased endoplasmic reticulum (ER) staining and ER calcium release in Panc-1 cells, and this was accompanied by increased expression of glucose related protein 78 and C/EBP homologous transcription factor (CHOP/GADD153) proteins. Similar results were observed after treatment with thapsigargin (Tg), a prototypical inducer of ER stress. The subsequent downstream effects of DIM/DIM-C-pPhtBu- and Tg-induced ER stress included CHOP-dependent induction of death receptor DR5 and subsequent cleavage of caspase 8, caspase 3, Bid and PARP. Activation of both receptor-dependent and receptor-independent (ER stress) pathways by DIM and DIM-C-pPhtBu in pancreatic cancer cells enhances the efficacy and potential clinical importance of these compounds for cancer chemotherapeutic applications.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Nutr.Home page
E. J. Kim, M. Shin, H. Park, J. E. Hong, H.-K. Shin, J. Kim, D. Y. Kwon, and J. H. Y. Park
Oral Administration of 3,3'-Diindolylmethane Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells in BALB/c Mice
J. Nutr., December 1, 2009; 139(12): 2373 - 2379.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Banerjee, Z. Wang, D. Kong, and F. H. Sarkar
3,3'-Diindolylmethane Enhances Chemosensitivity of Multiple Chemotherapeutic Agents in Pancreatic Cancer
Cancer Res., July 1, 2009; 69(13): 5592 - 5600.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Prevention ResearchHome page
F. S. Khwaja, S. Wynne, I. Posey, and D. Djakiew
3,3'-Diindolylmethane Induction of p75NTR-Dependent Cell Death via the p38 Mitogen-Activated Protein Kinase Pathway in Prostate Cancer Cells
Cancer Prevention Research, June 1, 2009; 2(6): 566 - 571.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
N. Ichite, M. B. Chougule, T. Jackson, S. V. Fulzele, S. Safe, and M. Singh
Enhancement of Docetaxel Anticancer Activity by a Novel Diindolylmethane Compound in Human Non-Small Cell Lung Cancer
Clin. Cancer Res., January 15, 2009; 15(2): 543 - 552.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
David. L. Carbone, K. A. Popichak, J. A. Moreno, S. Safe, and R. B. Tjalkens
Suppression of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Nitric-Oxide Synthase 2 Expression in Astrocytes by a Novel Diindolylmethane Analog Protects Striatal Neurons against Apoptosis
Mol. Pharmacol., January 1, 2009; 75(1): 35 - 43.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
T. Inamoto, S. Papineni, S. Chintharlapalli, S.-D. Cho, S. Safe, and A. M. Kamat
1,1-Bis(3'-indolyl)-1-(p-chlorophenyl)methane activates the orphan nuclear receptor Nurr1 and inhibits bladder cancer growth
Mol. Cancer Ther., December 1, 2008; 7(12): 3825 - 3833.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
P. Lei, M. Abdelrahim, S. D. Cho, X. Liu, and S. Safe
Structure-dependent activation of endoplasmic reticulum stress-mediated apoptosis in pancreatic cancer by 1,1-bis(3'-indoly)-1-(p-substituted phenyl)methanes
Mol. Cancer Ther., October 1, 2008; 7(10): 3363 - 3372.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
R.-Y. Su, K.-H. Chi, D.-Y. Huang, M.-H. Tai, and W.-W. Lin
15-deoxy-{Delta}12,14-prostaglandin J2 up-regulates death receptor 5 gene expression in HCT116 cells: involvement of reactive oxygen species and C/EBP homologous transcription factor gene transcription
Mol. Cancer Ther., October 1, 2008; 7(10): 3429 - 3440.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. Zou, P. Yue, F. R. Khuri, and S.-Y. Sun
Coupling of Endoplasmic Reticulum Stress to CDDO-Me-Induced Up-regulation of Death Receptor 5 via a CHOP-Dependent Mechanism Involving JNK Activation
Cancer Res., September 15, 2008; 68(18): 7484 - 7492.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y.-D. Lin, S. Chen, P. Yue, W. Zou, D. M. Benbrook, S. Liu, T. C. Le, K. D. Berlin, F. R. Khuri, and S.-Y. Sun
CAAT/Enhancer Binding Protein Homologous Protein-Dependent Death Receptor 5 Induction Is a Major Component of SHetA2-Induced Apoptosis in Lung Cancer Cells
Cancer Res., July 1, 2008; 68(13): 5335 - 5344.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
S. D. Cho, S. Chintharlapalli, M. Abdelrahim, S. Papineni, S. Liu, J. Guo, P. Lei, A. Abudayyeh, and S. Safe
5,5'-Dibromo-bis(3'-indolyl)methane induces Kruppel-like factor 4 and p21 in colon cancer cells
Mol. Cancer Ther., July 1, 2008; 7(7): 2109 - 2120.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
S. Ali, S. Banerjee, A. Ahmad, B. F. El-Rayes, P. A. Philip, and F. H. Sarkar
Apoptosis-inducing effect of erlotinib is potentiated by 3,3'-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer
Mol. Cancer Ther., June 1, 2008; 7(6): 1708 - 1719.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
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]

Home page
 Cancer Res.Home page
Y.-C. Wang, S. K. Kulp, D. Wang, C.-C. Yang, A. M. Sargeant, J.-H. Hung, Y. Kashida, M. Yamaguchi, G.-D. Chang, and C.-S. Chen
Targeting Endoplasmic Reticulum Stress and Akt with OSU-03012 and Gefitinib or Erlotinib to Overcome Resistance to Epidermal Growth Factor Receptor Inhibitors
Cancer Res., April 15, 2008; 68(8): 2820 - 2830.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Lu, L. Xia, H. Hua, and Y. Jing
Acetyl-Keto-{beta}-Boswellic Acid Induces Apoptosis through a Death Receptor 5-Mediated Pathway in Prostate Cancer Cells
Cancer Res., February 15, 2008; 68(4): 1180 - 1186.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
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]

Home page
 J. Nutr.Home page
H. J. Cho, M. R. Seon, Y. M. Lee, J. Kim, J.-K. Kim, S. G. Kim, and J. H. Y. Park
3,3'-Diindolylmethane Suppresses the Inflammatory Response to Lipopolysaccharide in Murine Macrophages
J. Nutr., January 1, 2008; 138(1): 17 - 23.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
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]

Home page
 Mol. Pharmacol.Home page
S. Chen, X. Liu, P. Yue, A. H. Schonthal, F. R. Khuri, and S.-Y. Sun
CCAAT/Enhancer Binding Protein Homologous Protein-Dependent Death Receptor 5 Induction and Ubiquitin/Proteasome-Mediated Cellular FLICE-Inhibitory Protein Down-Regulation Contribute to Enhancement of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis by Dimethyl-Celecoxib in Human Non Small-Cell Lung Cancer Cells
Mol. Pharmacol., November 1, 2007; 72(5): 1269 - 1279.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S.-Y. Sun, X. Liu, W. Zou, P. Yue, A. I. Marcus, and F. R. Khuri
The Farnesyltransferase Inhibitor Lonafarnib Induces CCAAT/Enhancer-binding Protein Homologous Protein-dependent Expression of Death Receptor 5, Leading to Induction of Apoptosis in Human Cancer Cells
J. Biol. Chem., June 29, 2007; 282(26): 18800 - 18809.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
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]

Home page
 Cancer Res.Home page
S. D. Cho, K. Yoon, S. Chintharlapalli, M. Abdelrahim, P. Lei, S. Hamilton, S. Khan, S. K. Ramaiah, and S. Safe
Nur77 Agonists Induce Proapoptotic Genes and Responses in Colon Cancer Cells through Nuclear Receptor-Dependent and Nuclear Receptor-Independent Pathways
Cancer Res., January 15, 2007; 67(2): 674 - 683.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
E. J. Kim, S. Y. Park, H.-K. Shin, D. Y. Kwon, Y.-J. Surh, and J. H. Y. Park
Activation of Caspase-8 Contributes to 3,3'-Diindolylmethane-Induced Apoptosis in Colon Cancer Cells
J. Nutr., January 1, 2007; 137(1): 31 - 36.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
S. Zhang, Z. Li, X. Wu, Q. Huang, H.-M. Shen, and C.-N. Ong
Methyl-3-indolylacetate inhibits cancer cell invasion by targeting the MEK1/2-ERK1/2 signaling pathway
Mol. Cancer Ther., December 1, 2006; 5(12): 3285 - 3293.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
P. Lei, M. Abdelrahim, and S. Safe
1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit ovarian cancer cell growth through peroxisome proliferator-activated receptor-dependent and independent pathways.
Mol. Cancer Ther., September 1, 2006; 5(9): 2324 - 2336.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
I. Kaddour-Djebbar, V. Lakshmikanthan, R. B. Shirley, Y. Ma, R. W. Lewis, and M. V. Kumar
Therapeutic advantage of combining calcium channel blockers and TRAIL in prostate cancer.
Mol. Cancer Ther., August 1, 2006; 5(8): 1958 - 1966.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.