Skip Navigation


Carcinogenesis Advance Access originally published online on December 20, 2006
Carcinogenesis 2007 28(5):1058-1066; doi:10.1093/carcin/bgl251
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
28/5/1058    most recent
bgl251v1
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 (2)
Google Scholar
Right arrow Articles by Jin, C.-Y.
Right arrow Articles by Kim, G.-Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jin, C.-Y.
Right arrow Articles by Kim, G.-Y.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Sulforaphane sensitizes tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis through downregulation of ERK and Akt in lung adenocarcinoma A549 cells

Cheung-Yun Jin{dagger}, Dong-Oh Moon1,{dagger}, Jae-Dong Lee, Moon-Soo Heo1, Yung Hyun Choi2, Chang-Min Lee3, Yeong-Min Park3 and Gi-Young Kim1,*

Department of Microbiology, Pusan National University, Busan 614-052, South Korea
1 Faculty of Applied Marine Science, Cheju National University, Jeju 690-756, South Korea
2 Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, South Korea
3 Department of Microbiology and Immunology and National Research Laboratory of Dendritic Cell Differentiation and Regulation, and Medical Research Institute, Pusan National University College of Medicine, Busan 602-739, South Korea

* To whom correspondence should be addressed. Tel: +82 64 754 3427; Fax: +82 64 756 3493; Email: immunkim{at}cheju.ac.kr

Correspondence may also be addressed to Y.-M.Park. Tel: +82 51 243 2259; Fax: +82 51 256 2269; Email: immunpym{at}pusan.ac.kr

The cytotoxic effect of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is limited in some cancer cells, including A549 lung adenocarcinoma cells. However, treatment with TRAIL in combination with subtoxic concentrations of sulforaphane (SFN) sensitizes TRAIL-resistant A549 cells to TRAIL-mediated apoptosis. Combined treatment with SFN and TRAIL induced chromatin condensation, DNA fragmentation, annexin V staining and sub-G1 phase DNA content. These indicators of apoptosis correlate with the induction of caspase-3 activity that results in the cleavage of poly(ADP-ribose) polymerase and the release of lactate dehydrogenase. Both the cytotoxic effect and apoptotic characteristics induced by combined treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, demonstrating the important role of caspase-3 in the observed cytotoxic effect. Combined treatment also triggered the activation of p38 MAPK and JNK, and downregulation of ERK and Akt. Inhibitors of ERK (PD98059) or Akt (LY294002), but not p38 MAPK, resulted in significantly decreased cell viability. Although the activation of JNK was increased in response to combined treatment, inhibition of the JNK pathway significantly attenuated cell viability. These results indicate that caspase-3 is a key regulator of apoptosis in response to combined SFN and TRAIL in human lung adenocarcinoma A549 cells through downregulation of ERK and Akt.

Abbreviations: DAPI, 4, 6-diamidino-2-phenylindole; DMSO, dimethyl sulfoxide; MTT, 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphnyl-2H-tetrazolium bromide; NSCLC, non-small cell lung cancer; PARP, poly(ADP-ribose) polymerase; PI, propidium iodide; PI3K, phosphoinositide 3-kinase; SDS–PAGE, sodium dodecyl sulfate–polyacrylamide gel electrophoresis; SFN, sulforaphane; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand

{dagger} These authors contributed equally to this work.

Received June 26, 2006; revised November 29, 2006; accepted December 7, 2006.


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
 Molecular Cancer TherapeuticsHome page
J. Voortman, T. P. Resende, M. A.I. Abou El Hassan, G. Giaccone, and F. A.E. Kruyt
TRAIL therapy in non-small cell lung cancer cells: sensitization to death receptor-mediated apoptosis by proteasome inhibitor bortezomib
Mol. Cancer Ther., July 1, 2007; 6(7): 2103 - 2112.
[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.