|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 May 2002, Vol. 99, No. 10, pp. 3771-3779
NEOPLASIA
Antitumorigenic effects of HIV protease inhibitor ritonavir:
inhibition of Kaposi sarcoma
Shibani Pati,
Colleen B. Pelser,
Joseph Dufraine,
Joseph L. Bryant,
Marvin S. Reitz Jr, and
Frank F. Weichold
From the Institute of Human Virology, University of
Maryland Biotechnology Institute; Department of Microbiology and
Immunology, University of Maryland; and Department of Biology, Morgan
State University, Baltimore, MD.
Treatment of patients with human immunodeficiency virus (HIV)
protease inhibitors such as ritonavir can result in increases in
CD4+ T-cell counts that are independent of a reduction in
HIV-1 viral load. This lack of correlation between the 2 has led to the
identification of additional effects of ritonavir that potentially
alter HIV disease pathogenesis. Our previous studies indicated that
ritonavir directly affects immune cell activation, proliferation, and
susceptibility to apoptosis. We show here that ritonavir inhibited the
activation and proliferation of primary endothelial cells and decreased
the production of tumor necrosis factor  (TNF-) interleukin 6 (IL-6), IL-8, and vascular endothelial growth factor, factors that all contribute to tumor neovascularization and to the development of Kaposi
sarcoma (KS) lesions. Ritonavir also suppressed the expression of
vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and E-selectin, which correlated with a functional decrease in
leukocyte adhesion. Transcriptional activation of nuclear factor- B,
as induced by the KS-promoting factor TNF-, the HIV-1 Tat protein,
or the human herpesvirus 8 protein ORF74, was inhibited by ritonavir.
KS-derived cell lines underwent apoptosis in vitro after treatment with
ritonavir at concentrations that are obtained in clinical therapy (3-15 µM). In a KS mouse xenotransplantation model, ritonavir inhibited
tumor formation and progression by KS-derived cells. Taken together,
these data suggest that ritonavir has antineoplastic effects that are
independent from its ability to inhibit the HIV protease.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Kraus, E. Malenke, J. Gogel, H. Muller, T. Ruckrich, H. Overkleeft, H. Ovaa, E. Koscielniak, J. T. Hartmann, and C. Driessen
Ritonavir induces endoplasmic reticulum stress and sensitizes sarcoma cells toward bortezomib-induced apoptosis
Mol. Cancer Ther.,
July 1, 2008;
7(7):
1940 - 1948.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Pyrko, A. Kardosh, W. Wang, W. Xiong, A. H. Schonthal, and T. C. Chen
HIV-1 Protease Inhibitors Nelfinavir and Atazanavir Induce Malignant Glioma Death by Triggering Endoplasmic Reticulum Stress
Cancer Res.,
November 15, 2007;
67(22):
10920 - 10928.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. I. de Silva, F. A. Post, M. D. Griffin, and D. H. Dockrell
HIV-1 Infection and the Kidney: An Evolving Challenge in HIV Medicine
Mayo Clin. Proc.,
September 1, 2007;
82(9):
1103 - 1116.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. C. Cuneo, T. Tu, L. Geng, A. Fu, D. E. Hallahan, and C. D. Willey
HIV Protease Inhibitors Enhance the Efficacy of Irradiation
Cancer Res.,
May 15, 2007;
67(10):
4886 - 4893.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Jiang, P. J. Mikochik, J. H. Ra, H. Lei, K. T. Flaherty, J. D. Winkler, and F. R. Spitz
HIV Protease Inhibitor Nelfinavir Inhibits Growth of Human Melanoma Cells by Induction of Cell Cycle Arrest
Cancer Res.,
February 1, 2007;
67(3):
1221 - 1227.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Srirangam, R. Mitra, M. Wang, J. C. Gorski, S. Badve, L. Baldridge, J. Hamilton, H. Kishimoto, J. Hawes, L. Li, et al.
Effects of HIV Protease Inhibitor Ritonavir on Akt-Regulated Cell Proliferation in Breast Cancer
Clin. Cancer Res.,
March 15, 2006;
12(6):
1883 - 1896.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Z. Dewan, J.-n. Uchihara, K. Terashima, M. Honda, T. Sata, M. Ito, N. Fujii, K. Uozumi, K. Tsukasaki, M. Tomonaga, et al.
Efficient intervention of growth and infiltration of primary adult T-cell leukemia cells by an HIV protease inhibitor, ritonavir
Blood,
January 15, 2006;
107(2):
716 - 724.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Bourlier, A. Zakaroff-Girard, S. De Barros, C. Pizzacalla, V. D. de Saint Front, M. Lafontan, A. Bouloumie, and J. Galitzky
Protease Inhibitor Treatments Reveal Specific Involvement of Matrix Metalloproteinase-9 in Human Adipocyte Differentiation
J. Pharmacol. Exp. Ther.,
March 1, 2005;
312(3):
1272 - 1279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bower, N. McCall-Peat, N. Ryan, L. Davies, A. M. Young, S. Gupta, M. Nelson, B. Gazzard, and J. Stebbing
Protease inhibitors potentiate chemotherapy-induced neutropenia
Blood,
November 1, 2004;
104(9):
2943 - 2946.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ikezoe, Y. Hisatake, T. Takeuchi, Y. Ohtsuki, Y. Yang, J. W. Said, H. Taguchi, and H. P. Koeffler
HIV-1 Protease Inhibitor, Ritonavir: A Potent Inhibitor of CYP3A4, Enhanced the Anticancer Effects of Docetaxel in Androgen-Independent Prostate Cancer Cells In vitro and In vivo
Cancer Res.,
October 15, 2004;
64(20):
7426 - 7431.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Waters, J. Stebbing, R. Jones, C. Michailidis, S. Sawleshwarkar, S. Mandalia, M. Bower, M. Nelson, and B. Gazzard
A comparison of the CD4 response to antiretroviral regimens in patients commencing therapy with low CD4 counts
J. Antimicrob. Chemother.,
August 1, 2004;
54(2):
503 - 507.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Stebbing, B. Gazzard, S. Mandalia, A. Teague, A. Waterston, V. Marvin, M. Nelson, and M. Bower
Antiretroviral Treatment Regimens and Immune Parameters in the Prevention of Systemic AIDS-Related Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
June 1, 2004;
22(11):
2177 - 2183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ikezoe, T. Saito, K. Bandobashi, Y. Yang, H. P. Koeffler, and H. Taguchi
HIV-1 protease inhibitor induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2
Mol. Cancer Ther.,
April 1, 2004;
3(4):
473 - 479.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Nasti, R. Talamini, A. Antinori, F. Martellotta, G. Jacchetti, F. Chiodo, G. Ballardini, L. Stoppini, G. Di Perri, M. Mena, et al.
AIDS-Related Kaposi's Sarcoma: Evaluation of Potential New Prognostic Factors and Assessment of the AIDS Clinical Trial Group Staging System in the Haart Era--the Italian Cooperative Group on AIDS and Tumors and the Italian Cohort of Patients Naive From Antiretrovirals
J. Clin. Oncol.,
August 1, 2003;
21(15):
2876 - 2882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Monini, C. Sgadari, G. Barillari, and B. Ensoli
HIV protease inhibitors: antiretroviral agents with anti-inflammatory, anti-angiogenic and anti-tumour activity
J. Antimicrob. Chemother.,
February 1, 2003;
51(2):
207 - 211.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gaedicke, E. Firat-Geier, O. Constantiniu, M. Lucchiari-Hartz, M. Freudenberg, C. Galanos, and G. Niedermann
Antitumor Effect of the Human Immunodeficiency Virus Protease Inhibitor Ritonavir: Induction of Tumor-Cell Apoptosis Associated with Perturbation of Proteasomal Proteolysis
Cancer Res.,
December 1, 2002;
62(23):
6901 - 6908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Pajonk, J. Himmelsbach, K. Riess, A. Sommer, and W. H. McBride
The Human Immunodeficiency Virus (HIV)-1 Protease Inhibitor Saquinavir Inhibits Proteasome Function and Causes Apoptosis and Radiosensitization in Non-HIV-associated Human Cancer Cells
Cancer Res.,
September 15, 2002;
62(18):
5230 - 5235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
