Enhancement by cyclosporin A of taxol-induced apoptosis of human urinary bladder cancer cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-05

AUTHORS

Takeo Nomura, Hideyuki Yamamoto, Hiromitsu Mimata, Miki Shitashige, Futoshi Shibasaki, Eishichi Miyamoto, Yoshio Nomura

ABSTRACT

Taxol is a microtubule-stabilizing agent which induces apoptosis in various cancer cells. In this study, we found that T24 cells derived from high grade human urinary bladder cancer were relatively resistant to taxol and that the IC50 value determined by a colorimetric WST-1 assay was 406.0 nM. Interestingly, cyclosporin A (CsA), an immunosuppressive drug, dramatically enhanced sensitivity to taxol, and the IC50 value was decreased to 47.5 nM in the presence of 1 microM CsA. KK47 cells derived from low grade human urinary bladder cancer showed high sensitivity to taxol with an IC50 value of 78.8 nM which decreased to 14.4 nM in the presence of 1 microM CsA. FK506, another immunosuppressive drug, also enhanced sensitivity to taxol. Furthermore, a concomitant loss of calcineurin activity was observed after the treatment of both cell lines with both CsA and FK506. Taxol induced apoptosis of the cells, as assessed by Hoechst 33258 staining and by the measurement of caspase 3 activity. Immunoblot analysis with an antibody against Bcl-2 phosphorylated at serine 70 demonstrated that taxol induced the phosphorylation of Bcl-2 with its enhancement in the presence of CsA. In addition, treatment of the cells with CsA significantly decreased the expression of Bcl-2 at both the protein and mRNA levels. These results suggest that the enhancement of taxol-induced apoptosis by immunosuppressive drugs is at least partly due to the inhibition of calcineurin activity and the loss of the antiapoptotic function of Bcl-2 via the enhancement of phosphorylation and the reduction of expression. More... »

PAGES

102-111

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00240-002-0239-4

DOI

http://dx.doi.org/10.1007/s00240-002-0239-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1029549814

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12086014


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00240-002-0239-4'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00240-002-0239-4'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00240-002-0239-4'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00240-002-0239-4'


 

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