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

1 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. 2 Aspirin at a plasma-attainable and nontoxic level suppressed the proliferation of B16 cells. 3 Aspirin induced the activation of p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases. 4 Inhibition of JNK, but not p38, decreased the suppressive effect of aspirin upon the proliferation of B16 cells. 5 The aspirin-induced reduction in B16 proliferation was cumulative over time. 6 Aspirin and the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) induced B16 cell death synergistically. 7 In addition to the murine B16 cell line, the proliferation of SK-28 human melanoma cells was also suppressed by aspirin. 8 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.705163.