Curcumin induces c-jun N-terminal kinase-dependent apoptosis in HCT116 human colon cancer cells.
Curcumin, the major pigment of the dietary spice turmeric has the potential for chemoprevention by promotion of apoptosis. Mitogen-activated protein kinase (MAPK) and NF-kappa B (NFkappaB) signalling cascades are thought to regulate apoptosis and cell survival. While curcumin inhibits NFkappaB, its effects upon the MAPK pathways are unclear. This study investigates curcumin effects upon MAPK signalling and apoptosis in HCT116 cells. Here we report that curcumin time- and dose-dependent induction of apoptosis were accompanied by sustained phosphorylation and activation of c-jun N-terminal kinase (JNK) and p38 MAPK as well as inhibition of constitutive NFkappaB transcriptional activity. Curcumin treatment also induced JNK-dependent sustained phosphorylation of c-jun and stimulation of AP-1 transcriptional activity. Curcumin-mediated c-jun phosphorylation and apoptosis were reduced by treatment with the JNK-specific inhibitor SP600125. Conversely, the p38-specific inhibitor SB203580 had no effect upon curcumin-induced apoptosis. Curcumin treatment had no effect on the activity of extracellular signal-regulated protein kinase (ERK). Taken together, our data show for the first time that JNK, but not p38 or ERK signalling, plays an important role in curcumin-mediated apoptosis in human colon cancer cells that may underlie its chemopreventive effects.
Collett
Gavin P
GP
Department of Surgery, The Cancer Centre, Queen's University Belfast, Belfast BT12 6BJ, UK.
Campbell
Frederick Charles
FC
D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D003474:Curcumin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D000873:Anthracenes; D004791:Enzyme Inhibitors; D007093:Imidazoles; D016328:NF-kappa B; D011725:Pyridines; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D003474:Curcumin; C093642:SB 203580