title: Stress-responsive JNK mitogen-activated protein kinase mediates aspirin-induced suppression of B16 melanoma cellular proliferation.
abstract: 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.
authors.affiliation: Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Ordan
authors.forename: Ronit
authors.initials: R
authors.lastname: Rotem
authors.forename: Ilona
authors.initials: I
authors.lastname: Jaspers
authors.forename: Eliezer
authors.initials: E
authors.lastname: Flescher
mesh_terms: 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
chemical_list: D016588:Anticarcinogenic Agents; D010755:Organophosphates; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D001241:Aspirin