Stress‐responsive JNK mitogen‐activated protein kinase mediates aspirin‐induced suppression of B16 melanoma cellular proliferation

Available anticancer drugs do not seem to modify the prognosis of metastatic melanoma. Salicylate and acetyl salicylic acid (aspirin) were found to suppress growth in a number of transformed cells, that is, prostate and colon. Therefore, we studied the direct effects of aspirin on metastatic B16 mel...

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Bibliographic Details
Published in:British journal of pharmacology 2003-03, Vol.138 (6), p.1156-1162
Main Authors: Ordan, Orly, Rotem, Ronit, Jaspers, Ilona, Flescher, Eliezer
Format: Article
Language:English
Subjects:
Anticarcinogenic Agents - metabolism
aspirin
Aspirin - pharmacology
BCNU
Biological and medical sciences
Cell Death - drug effects
Drug Synergism
Genes, jun - drug effects
Genes, jun - genetics
Humans
JNK
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase 4
MAPK
Medical sciences
melanoma
Melanoma, Experimental - pathology
Mitogen-Activated Protein Kinase Kinases - metabolism
Organophosphates - metabolism
p38
Suppression, Genetic - drug effects
Suppression, Genetic - genetics
Tumor Cells, Cultured
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Summary:Available anticancer drugs do not seem to modify the prognosis of metastatic melanoma. Salicylate and acetyl salicylic acid (aspirin) were found to suppress growth in a number of transformed cells, that is, prostate and colon. Therefore, we studied the direct effects of aspirin on metastatic B16 melanoma cells. Aspirin at a plasma‐attainable and nontoxic level suppressed the proliferation of B16 cells. Aspirin induced the activation of p38 and c‐Jun N‐terminal kinase (JNK) mitogen‐activated protein kinases. Inhibition of JNK, but not p38, decreased the suppressive effect of aspirin upon the proliferation of B16 cells. The aspirin‐induced reduction in B16 proliferation was cumulative over time. Aspirin and the chemotherapeutic drug 1,3‐bis(2‐chloroethyl)‐1‐nitrosourea (BCNU) induced B16 cell death synergistically. In addition to the murine B16 cell line, the proliferation of SK‐28 human melanoma cells was also suppressed by aspirin. In conclusion, aspirin suppresses the proliferation of metastatic B16 cells in a JNK‐dependent mechanism. British Journal of Pharmacology (2003) 138, 1156–1162. doi:10.1038/sj.bjp.0705163
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0705163