Curcumin inhibits UV irradiation-induced oxidative stress and apoptotic biochemical changes in human epidermoid carcinoma A431 cells.
Ultraviolet (UV) light is a strong apoptotic trigger that induces caspase-dependent biochemical changes in cells. Previously we showed that UV irradiation can activate caspase-3, and the subsequent cleavage and activation of p21(Cdc42/Rac)-activated kinase 2 (PAK2) in human epidermoid carcinoma A431 cells. In this study we demonstrate that curcumin (Cur), the yellow pigment of Curcuma longa with known anti-oxidant and anti-inflammatory properties, can prevent UV irradiation-induced apoptotic changes, including c-Jun N-terminal kinase (JNK) activation, loss of mitochondrial membrane potential (MMP), mitochondrial release of cytochrome C, caspase-3 activation, and cleavage/activation of PAK2 in A431 cells. Flow cytometric analysis using the cell permeable dye 2',7'-dichlorofluorescin diacetate (DCF-DA) as an indicator of reactive oxygen species (ROS) generation revealed that the increase in intracellular oxidative stress caused by UV irradiation could be abolished by Cur. In addition, we found that SP600125, a JNK-specific inhibitor, reduced UV irradiation-induced JNK activation as well as caspase-3 activation, indicating that JNK activity is required for UV irradiation-induced caspase activation. Collectively, our results demonstrate that Cur significantly attenuates UV irradiation-induced ROS formation, and suggest that ROS triggers JNK activation, which in turn causes MMP change, cytochrome C release, caspase activation, and subsequent apoptotic biochemical changes.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005452:Fluoresceins; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D054462:p21-Activated Kinases
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005452:Fluoresceins; D017382:Reactive Oxygen Species; C029569:diacetyldichlorofluorescein; D045304:Cytochromes c; C515907:PAK2 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003474:Curcumin