help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
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 Google Scholar
Google Scholar
Right arrow Articles by RUBINS, J. B.
Right arrow Articles by BITTERMAN, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by RUBINS, J. B.
Right arrow Articles by BITTERMAN, P.

Am. J. Respir. Crit. Care Med., Volume 157, Number 5, May 1998, 1616-1622

Lovastatin Induces Apoptosis in Malignant Mesothelioma Cells

JEFFREY B. RUBINS, TODD GREATENS, ROBERT A. KRATZKE, ANNIE T. TAN, VITALY A. POLUNOVSKY, and PETER BITTERMAN

Department of Medicine, Veterans Affairs Medical Center, and Department of Medicine, University of Minnesota, Minneapolis

Malignant mesothelioma causes profound morbidity and nearly universal mortality that is refractory to conventional treatment with aggressive surgery, radiotherapy, or chemotherapy. We report that pharmacologic concentrations of lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, induced apoptosis in human malignant mesothelioma cell lines. Mesothelioma cell viability was decreased in a dose-dependent manner by lovastatin (5 to 30 µM). These effects were not reversed by exogenous growth factors or cholesterol, but were reversed by addition of 100 µM mevalonate, confirming that lovastatin affected mesothelioma viability by inhibiting mevalonate synthesis. Lovastatin appeared to decrease mesothelioma viability by inducing apoptosis, as indicated by morphologic changes, histologic evidence of nuclear condensation and degeneration, and flow-cytometric analysis of DNA content. Lovastatin's effects on cell viability were partially reversed in the presence of farnesol, and treatment of mesothelioma cells with a specific farnesyl-protein transferase (FTP) inhibitor decreased cell viability and induced morphologic changes indistinguishable from those caused by lovastatin. In addition, lovastatin-treated cells showed translocation of ras guanosine triphosphate (GTP)-binding proteins from membrane to cytosolic fractions on Western blots, suggesting that lovastatin's effects on mesothelioma were mediated in part by disrupting acylation of GTP-binding proteins. Thus, lovastatin is a commercially available and clinically well-tolerated agent that reduces viability and induces apoptosis of mesothelioma cells, and may provide the basis for adjunctive treatments of patients with mesothelioma.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
K. K. W. Chan, A. M. Oza, and L. L. Siu
The Statins as Anticancer Agents
Clin. Cancer Res., January 1, 2003; 9(1): 10 - 19.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
A. Wachtershauser, B. Akoglu, and J. Stein
HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell line Caco-2
Carcinogenesis, July 1, 2001; 22(7): 1061 - 1067.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. W.-L. Wong, M. M. Tan, Z. Xia, J. Dimitroulakos, M. D. Minden, and L. Z. Penn
Cerivastatin Triggers Tumor-specific Apoptosis with Higher Efficacy than Lovastatin
Clin. Cancer Res., July 1, 2001; 7(7): 2067 - 2075.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. Dimitroulakos, L. Y. Ye, M. Benzaquen, M. J. Moore, S. Kamel-Reid, M. H. Freedman, H. Yeger, and L. Z. Penn
Differential Sensitivity of Various Pediatric Cancers and Squamous Cell Carcinomas to Lovastatin-induced Apoptosis: Therapeutic Implications
Clin. Cancer Res., January 1, 2001; 7(1): 158 - 167.
[Abstract] [Full Text]

Home page
 Am. J. Respir. Crit. Care Med.Home page
N. NASREEN, K. A. MOHAMMED, P. A. DOWLING, M. J. WARD, G. GALFFY, and V. B. ANTONY
Talc Induces Apoptosis in Human Malignant Mesothelioma Cells In Vitro
Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): 595 - 600.
[Abstract] [Full Text]

Home page
 HypertensionHome page
A. Faggiotto and R. Paoletti
Statins and Blockers of the Renin-Angiotensin System : Vascular Protection Beyond Their Primary Mode of Action
Hypertension, October 1, 1999; 34(4): 987 - 996.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
J. W. Choi and S. E. Jung
Lovastatin-Induced Proliferation Inhibition and Apoptosis in C6 Glial Cells
J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 572 - 579.
[Abstract] [Full Text]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. TAN, H. LEVREY, C. DAHM, V. A. POLUNOVSKY, J. RUBINS, and P. B. BITTERMAN
Lovastatin Induces Fibroblast Apoptosis In Vitro and In Vivo . A Possible Therapy for Fibroproliferative Disorders
Am. J. Respir. Crit. Care Med., January 1, 1999; 159(1): 220 - 227.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 1998 American Thoracic Society 		  Solid Organ Transplant for the Intensivist 2008