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The role of Bcl-xL and nuclear factor-kappaB in the effect of taxol on the viability of dendritic cells.

Kim MH, Joo HG - J. Vet. Sci. (2009)

Bottom Line: Taxol has been used effectively in cancer therapies.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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Jeju National University, Jeju, Korea.

ABSTRACT
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.

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NF-κB involvement in the taxol-induced effects on dendritic cells (DCs). The mobilization of NF-κB p65 molecules in DCs was detected by staining with an anti-NF-κB p65 antibody and confocal microscopy. Arrows indicate the nuclei of DCs (A). In the inhibitor assay, the percentage of viable DCs was measured as described in Fig. 1 (B). Asterisk (*) and sharp (#) indicate p < 0.05 in the comparison of ContDCs vs TaxolDCs, TaxolDCs vs TaxolDCs + N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK), respectively. Representative data from three independent experiments are presented.
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Figure 4: NF-κB involvement in the taxol-induced effects on dendritic cells (DCs). The mobilization of NF-κB p65 molecules in DCs was detected by staining with an anti-NF-κB p65 antibody and confocal microscopy. Arrows indicate the nuclei of DCs (A). In the inhibitor assay, the percentage of viable DCs was measured as described in Fig. 1 (B). Asterisk (*) and sharp (#) indicate p < 0.05 in the comparison of ContDCs vs TaxolDCs, TaxolDCs vs TaxolDCs + N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK), respectively. Representative data from three independent experiments are presented.

Mentions: Using confocal microscopy, the mobilization of NF-κB p65 subunit molecules from the cytosol to the nucleus were much greater in TaxolDCs in comparison to ContDCs (Fig. 4A). Furthermore, TPCK, which is an inhibitor of the NF-κB pathway, significantly decreased the viability of TaxolDCs, but not that of ContDCs (Fig. 4B). These results suggest that taxol sustains DC survival via the NF-κB pathway.


The role of Bcl-xL and nuclear factor-kappaB in the effect of taxol on the viability of dendritic cells.

Kim MH, Joo HG - J. Vet. Sci. (2009)

NF-κB involvement in the taxol-induced effects on dendritic cells (DCs). The mobilization of NF-κB p65 molecules in DCs was detected by staining with an anti-NF-κB p65 antibody and confocal microscopy. Arrows indicate the nuclei of DCs (A). In the inhibitor assay, the percentage of viable DCs was measured as described in Fig. 1 (B). Asterisk (*) and sharp (#) indicate p < 0.05 in the comparison of ContDCs vs TaxolDCs, TaxolDCs vs TaxolDCs + N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK), respectively. Representative data from three independent experiments are presented.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2801113&req=5

Figure 4: NF-κB involvement in the taxol-induced effects on dendritic cells (DCs). The mobilization of NF-κB p65 molecules in DCs was detected by staining with an anti-NF-κB p65 antibody and confocal microscopy. Arrows indicate the nuclei of DCs (A). In the inhibitor assay, the percentage of viable DCs was measured as described in Fig. 1 (B). Asterisk (*) and sharp (#) indicate p < 0.05 in the comparison of ContDCs vs TaxolDCs, TaxolDCs vs TaxolDCs + N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK), respectively. Representative data from three independent experiments are presented.
Mentions: Using confocal microscopy, the mobilization of NF-κB p65 subunit molecules from the cytosol to the nucleus were much greater in TaxolDCs in comparison to ContDCs (Fig. 4A). Furthermore, TPCK, which is an inhibitor of the NF-κB pathway, significantly decreased the viability of TaxolDCs, but not that of ContDCs (Fig. 4B). These results suggest that taxol sustains DC survival via the NF-κB pathway.

Bottom Line: Taxol has been used effectively in cancer therapies.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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Jeju National University, Jeju, Korea.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus