Document Detail


Photoactivated hypericin is an anti-proliferative agent that induces a high rate of apoptotic death of normal, transformed, and malignant T lymphocytes: implications for the treatment of cutaneous lymphoproliferative and inflammatory disorders.
MedLine Citation:
PMID:  9699738     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypericin is a photodynamic compound activated by either visible (400-700 nm) or UVA (320-400 nm) light, and has been shown to inhibit the growth of a variety of neoplastic cell types. In this study, hypericin was found to inhibit proliferative responses of malignant T cells derived from the blood of patients with cutaneous T cell lymphoma. Control cells included peripheral blood mononuclear cells (PBMC) from normal volunteers or Epstein-Barr virus-transformed lymphocytes. Cells from each of these populations were incubated with serial dilutions of hypericin or 8-methoxypsoralen and then stimulated with the mitogen ConA (10 microg per ml). Cultures were prepared in the dark to minimize photoactivation of the hypericin. Proliferation was measured by [3H]thymidine labeling after 72 h. Hypericin, photoactivated with 1.1-3.3 J white light per cm2, inhibited cellular proliferation of malignant T cells with IC50 values from 0.34 to 0.53 microM, normal PBMC with IC50 values of 0.11-0.76 microM, and Epstein-Barr virus-transformed cells with IC50 values of 0.75-3.2 microM. UVA-photoactivated hypericin (0.5-2.0 J per cm2) could also inhibit proliferation with IC50 values of 0.57-1.8 microM, 0.7-4.6 microM, and 2.0-3.7 microM for malignant, normal, or Epstein-Barr virus-transformed cells, respectively. Hypericin, photoactivated with either UVA or white light, could induce near complete apoptosis (94%) in malignant cutaneous T cell lymphoma T cells, whereas lower levels of apoptosis (37-88%) were induced in normal PBMC. These data indicate that hypericin inhibits mitogen-induced proliferation of malignant T cells from patients with cutaneous T cell lymphoma, PBMC from normal individuals, as well as Epstein-Barr virus-transformed lymphocytes, and that inhibition of cell proliferation is dependent on the concentration of hypericin used and the dose of light required to photoactivate the compound. Induction of apoptosis is, in part, one mechanism by which photoactivated hypericin inhibits malignant T cell proliferation.
Authors:
F E Fox; Z Niu; A Tobia; A H Rook
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  111     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-08-19     Completed Date:  1998-08-19     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  327-32     Citation Subset:  IM    
Affiliation:
Department of Dermatology, University of Pennsylvania, Philadelphia 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cells, Cultured
Humans
Keratitis / drug therapy*
Lymphocyte Activation / drug effects*
Lymphoma, T-Cell, Cutaneous / drug therapy*
Methoxsalen / pharmacology
Perylene / analogs & derivatives*,  pharmacology,  therapeutic use
Photochemotherapy*
Skin Neoplasms / drug therapy*
T-Lymphocytes / drug effects*
Ultraviolet Rays
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 198-55-0/Perylene; 298-81-7/Methoxsalen; 548-04-9/hypericin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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