IOVS Health Education Research
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2006;47:3708-3716.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0119
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sareen, D.
Right arrow Articles by Polans, A. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sareen, D.
Right arrow Articles by Polans, A. S.

Mitochondria as the Primary Target of Resveratrol-Induced Apoptosis in Human Retinoblastoma Cells

Dhruv Sareen,1,2 Paul R. van Ginkel,2 Jennifer C. Takach,1,2 Ayesha Mohiuddin,2 Soesiawati R. Darjatmoko,2 Daniel M. Albert,2 and Arthur S. Polans1,2

1From the Departments of Biomolecular Chemistry and 2Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

PURPOSE. To determine the molecular mechanisms by which resveratrol induces retinoblastoma tumor cell death.

METHODS. After resveratrol treatment, Y79 tumor cell viability was measured using a fluorescence-based assay, and proapoptotic and antiproliferative effects were characterized by Hoechst stain and flow cytometry, respectively. Mitochondrial transmembrane potential ({Delta}{Psi}m) was measured as a function of drug treatment using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzamidazolocarbocyanin iodide (JC-1), whereas the release of cytochrome c from mitochondria was assayed by immunoblotting and caspase activities were determined by monitoring the cleavage of fluorogenic peptide substrates.

RESULTS. Resveratrol induced a dose- and time-dependent decrease in Y79 tumor cell viability and inhibited proliferation by inducing S-phase growth arrest and apoptotic cell death. Preceding cell death, resveratrol evoked a rapid dissipation of {Delta}{Psi}m. This was followed by the release of cytochrome c into the cytoplasm and a substantial increase in the activities of caspase-9 and caspase-3. Additionally, in a cell-free system, resveratrol directly induced the depolarization of isolated mitochondria.

CONCLUSIONS. These results demonstrate that resveratrol, a nontoxic natural plant compound, inhibits Y79 cell proliferation and stimulates apoptosis through activation of the mitochondrial (intrinsic) apoptotic pathway and may warrant further exploration as an adjuvant to conventional anticancer therapies for retinoblastoma.




This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
K. H. Lin, G. Hsiao, C. M. Shih, D. S. Chou, and J. R. Sheu
Mechanisms of resveratrol-induced platelet apoptosis
Cardiovasc Res, June 8, 2009; (2009) cvp139v2.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
P. R. van Ginkel, S. R. Darjatmoko, D. Sareen, L. Subramanian, S. Bhattacharya, M. J. Lindstrom, D. M. Albert, and A. S. Polans
Resveratrol Inhibits Uveal Melanoma Tumor Growth via Early Mitochondrial Dysfunction
Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1299 - 1306.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
D. Sareen, S. R. Darjatmoko, D. M. Albert, and A. S. Polans
Mitochondria, Calcium, and Calpain are Key Mediators of Resveratrol-Induced Apoptosis in Breast Cancer
Mol. Pharmacol., December 1, 2007; 72(6): 1466 - 1475.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. H. Heiss, Y. D. C. Schilder, and V. M. Dirsch
Chronic Treatment with Resveratrol Induces Redox Stress- and Ataxia Telangiectasia-mutated (ATM)-dependent Senescence in p53-positive Cancer Cells
J. Biol. Chem., September 14, 2007; 282(37): 26759 - 26766.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. R. van Ginkel, D. Sareen, L. Subramanian, Q. Walker, S. R. Darjatmoko, M. J. Lindstrom, A. Kulkarni, D. M. Albert, and A. S. Polans
Resveratrol Inhibits Tumor Growth of Human Neuroblastoma and Mediates Apoptosis by Directly Targeting Mitochondria
Clin. Cancer Res., September 1, 2007; 13(17): 5162 - 5169.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
A. A. Baran, K. A. Silverman, J. Zeskand, R. Koratkar, A. Palmer, K. McCullen, W. J. Curran Jr, T. B. Edmonston, L. D. Siracusa, and A. M. Buchberg
The modifier of Min 2 (Mom2) locus: Embryonic lethality of a mutation in the Atp5a1 gene suggests a novel mechanism of polyp suppression
Genome Res., May 1, 2007; 17(5): 566 - 576.
[Abstract] [Full Text] [PDF]

Home page
 J Ultrasound MedHome page
W. Luo, X. Zhou, X. Gong, M. Zheng, J. Zhang, and X. Guo
Study of Sequential Histopathologic Changes, Apoptosis, and Cell Proliferation in Rabbit Livers After High-Intensity Focused Ultrasound Ablation
J. Ultrasound Med., April 1, 2007; 26(4): 477 - 485.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the Association for Research in Vision and Ophthalmology