Bioenergetic modulation with dichloroacetate reduces the growth of melanoma cells and potentiates their response to BRAFV600E inhibition View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

Cecilie Abildgaard, Christina Dahl, Astrid L Basse, Tao Ma, Per Guldberg

ABSTRACT

BACKGROUND: Advances in melanoma treatment through targeted inhibition of oncogenic BRAF are limited owing to the development of acquired resistance. The involvement of BRAFV600E in metabolic reprogramming of melanoma cells provides a rationale for co-targeting metabolism as a therapeutic approach. METHODS: We examined the effects of dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, on the growth and metabolic activity of human melanoma cell lines. The combined effect of DCA and the BRAF inhibitor vemurafenib was investigated in BRAFV600E -mutated melanoma cell lines. Vemurafenib-resistant cell lines were established in vitro and their sensitivity to DCA was tested. RESULTS: DCA induced a reduction in glycolytic activity and intracellular ATP levels, and inhibited cellular growth. Co-treatment of BRAFV600E-mutant melanoma cells with DCA and vemurafenib induced a greater reduction in intracellular ATP levels and cellular growth than either compound alone. In addition, melanoma cells with in vitro acquired resistance to vemurafenib retained their sensitivity to DCA. CONCLUSIONS: These results suggest that DCA potentiates the effect of vemurafenib through a cooperative attenuation of energy production. Furthermore, the demonstration of retained sensitivity to DCA in melanoma cells with acquired resistance to vemurafenib could have implications for melanoma treatment. More... »

PAGES

247

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12967-014-0247-5

DOI

http://dx.doi.org/10.1186/s12967-014-0247-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020114193

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25182332


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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.10.1186/s12967-014-0247-5'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12967-014-0247-5'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12967-014-0247-5'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12967-014-0247-5'


 

This table displays all metadata directly associated to this object as RDF triples.

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