J Vet Sci.  2003 Dec;4(3):229-234.

Altered maturation of dendritic cells by taxol, an anticancer drug

• Joo HG

Abstract

Taxol is a clinically useful anticancer drug against a variety of cancers. Although it has been known that taxol induces the apoptosis of cancer cells through cytochrome C release and the activation of caspases, the effect of taxol on dendritic cells (DCs) has not been studied. In this study, taxol enhanced the expression of MHC class II on DCs, compared to medium-treated immature DCs. Surprisingly, the viability of DCs was not decreased by taxol, whereas that of cancer cells was. It was confirmed that taxol did not induce the apoptosis of DCs based on annexin V-FITC/propidium iodide (PI) staining assay. Since previous study demonstrated that taxol induced the production of nitric oxide (NO) related to the viability of DCs, the level of NO from taxol-treated DCs was determined. Any significant amount of NO was not detected. Although taxol enhanced the expression of a maturation marker, MHC class II molecules, it strikingly inhibited the proliferation of splenic T lymphocytes activated by DCs. Taken together, this study demonstrated that taxol induced an altered maturation of DCs, the increase of MHC class II molecule but the inhibition of proliferation of splenic T lymphocytes. It is suggested that taxol may induce the immunosuppression in patients with cancer by the inhibition of DC-activated T cell proliferation, but not by the direct killing of DCs.

Keyword

dendritic cells; taxol; maturation

MeSH Terms

Animals
Antineoplastic Agents, Phytogenic/*pharmacology
Apoptosis/drug effects
Coloring Agents/metabolism
Dendritic Cells/cytology/*drug effects/immunology
Female
Flow Cytometry
Formazans/metabolism
Histocompatibility Antigens Class II/biosynthesis
Lymphocyte Activation/drug effects
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Nitric Oxide/metabolism
Paclitaxel/*pharmacology
T-Lymphocytes/cytology/immunology/metabolism
Tetrazolium Salts/metabolism