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An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus
Published on: August 25, 2017
In vitro sensitivity of Kaposi's sarcoma cells to various chemotherapeutic agents including acyclic nucleoside
T Simonart1, G Andrei, D Parent
1Department of Dermatology, Erasme University Hospital, Brussels, Belgium.
Abstract:
The involvement of a viral agent in the pathogenesis of Kaposi's sarcoma (KS) points to antiviral agents as possible therapeutic and/or prophylactic options in the management of the disease. In the present study we investigated the antiproliferative effects of various chemotherapeutic agents, including acyclic nucleoside phosphonates, on the growth of KS-derived cells. Nested PCR amplification demonstrated that these cells do not contain human herpesvirus 8 (HHV-8) DNA sequences. The cytotoxicity of the chemotherapeutic compounds was less pronounced in KS cells than in human dermal microvascular endothelial cells, which are considered to be the normal counterpart of KS cells. Stimulation of KS cells with basic fibroblast growth factor (bFGF) and correction of the IC50 values by the doubling times revealed that the apparent chemotherapeutic resistance of KS cells could mainly be attributed to the long doubling times of these cells. bFGF-stimulated KS cells still exhibited no particular sensitivity to the acyclic nucleoside phosphonates whose activity extends to HHV-8, which is consistent with the absence of linear HHV-8 DNA synthesis in these cells. Our data suggest that neither anti-cancer agents nor antiviral agents such as the acyclic nucleoside phosphonates can discriminate efficiently between KS cells and normal endothelial cells.
Insights
Antiviral drugs like acyclic nucleoside phosphonates do not effectively target Kaposi
Area of Science:
- Oncology
- Virology
- Pharmacology
Background:
- Kaposi's sarcoma (KS) pathogenesis involves a viral agent, suggesting antiviral therapies.
- Human herpesvirus 8 (HHV-8) is implicated in KS development.
- Acyclic nucleoside phosphonates show activity against HHV-8.
Purpose of the Study:
- To investigate the antiproliferative effects of chemotherapeutic agents, including acyclic nucleoside phosphonates, on KS-derived cells.
- To determine if KS cells are sensitive to antiviral agents targeting HHV-8.
- To compare the efficacy of chemotherapeutic agents on KS cells versus normal endothelial cells.
Main Methods:
- Nested PCR amplification to detect HHV-8 DNA in KS cells.
- Cytotoxicity assays using various chemotherapeutic agents on KS cells and human dermal microvascular endothelial cells.
- Cell stimulation with basic fibroblast growth factor (bFGF) and IC50 value correction for doubling times.
Main Results:
- KS-derived cells lacked detectable HHV-8 DNA sequences.
- KS cells exhibited lower sensitivity to chemotherapeutic compounds compared to normal endothelial cells.
- Apparent chemotherapeutic resistance in KS cells was primarily due to their long doubling times.
- bFGF-stimulated KS cells showed no specific sensitivity to acyclic nucleoside phosphonates, consistent with absent HHV-8 DNA synthesis.
Conclusions:
- Acyclic nucleoside phosphonates do not effectively target KS cells, even when stimulated.
- Neither anti-cancer nor antiviral agents efficiently discriminate between KS cells and normal endothelial cells.
- The study questions the efficacy of current antiviral and chemotherapeutic strategies for KS management based on these findings.
