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.
Ordan
Orly
O
Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Rotem
Ronit
R
Jaspers
Ilona
I
Flescher
Eliezer
E
D016588:Anticarcinogenic Agents / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004357:Drug Synergism; D016758:Genes, jun / Q000187:drug effects / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D008546:Melanoma, Experimental / Q000473:pathology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010755:Organophosphates / Q000378:metabolism; D013489:Suppression, Genetic / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D010755:Organophosphates; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D001241:Aspirin