The role of Bcl-xL and nuclear factor-kappaB in the effect of taxol on the viability of dendritic cells.
Taxol has been used effectively in cancer therapies. Our previous study demonstrated that taxol induced altered maturation and improved viability of dendritic cells (DCs). However, the effects of taxol on DC viability have not been fully elucidated. In the present study, flow cytometric analyses revealed that taxol treatment significantly increased the number of viable DCs and the expression levels of a representative anti-apoptotic protein Bcl-xL. Furthermore, mobilization of the p65 subunit of nuclear factor-kappaB (NF-kappaB) from the cytosol to the nucleus in DCs was observed by confocal microscopy. An inhibition assay using N-p-tosyl-(L)-phenylalanine chloromethyl ketone confirmed that NF-kappaB was intimately involved in the effects of taxol on DC viability. In addition, we investigated the mechanisms of taxol enhancement of DC viability. Since taxol is a popular anticancer agent used in clinic, this study may provide a rationale for the use of taxol in DC immunotherapy to treat cancer patients. Taken together, these results confirm that taxol increases DC viability, and this information may provide new insights for new clinical applications of both taxol and DCs.
Kim
Mi Hyoung
MH
Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Jeju National University, Jeju, Korea.
Joo
Hong Gu
HG
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D017239:Paclitaxel / Q000494:pharmacology*; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D051020:bcl-X Protein / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; C494812:Bcl2l1 protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D018664:Interleukin-12; D014108:Tosylphenylalanyl Chloromethyl Ketone; D017239:Paclitaxel