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

摘要

class="enumerated" style="list-style-type:decimal">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.