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Stress‐responsive JNK mitogen‐activated protein kinase mediates aspirin‐induced suppression of B16 melanoma cellular proliferation
Author(s) -
Ordan Orly,
Rotem Ronit,
Jaspers Ilona,
Flescher Eliezer
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705163
Subject(s) - aspirin , p38 mitogen activated protein kinases , mitogen activated protein kinase , cell growth , salicylic acid , kinase , cancer research , melanoma , protein kinase a , chemistry , pharmacology , medicine , microbiology and biotechnology , biology , biochemistry
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