Altered maturation of dendritic cells by taxol, an anticancer drug.
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.
Joo
Hong-Gu
HG
Department of Veterinary Medicine, Cheju National University, Jeju 690-756, Korea. jooh@cheju.ac.kr
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004396:Coloring Agents / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005562:Formazans / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D005562:Formazans; D000949:Histocompatibility Antigens Class II; D013778:Tetrazolium Salts; C079782:MTT formazan; D009569:Nitric Oxide; D017239:Paclitaxel