Activation of several concurrent proapoptic pathways by sulforaphane in human colon cancer cells SW620.
Despite the reported cytotoxicity and apoptosis-inducing properties of sulforaphane (SF) in colon cancer cells, the details concerning individual mechanisms and signaling cascades underlying SF-mediated apoptosis remain unclear. To understand different aspects of SF-induced proapoptic signaling in advanced colon carcinoma, we investigated its mechanisms in metastatic SW620 cell line. Our results indicate that in SW620 cells SF acts to induce multivariate cascades including DNA-damage response pathway whose proapoptotic signaling is nevertheless reduced owing to the mutant status of p53 and caspase-2-JNK pathway which seems to complement and enhance p53-dependent signaling, however only in wild-type p53. Furthermore, both pathways require the active role of mitochondria and do not depend on generation of ROS, making SF an attractive chemopreventive agent whose antitumor properties should be further investigated in colon cancer.
Rudolf
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Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Simkova 870, Hradec Kralove, Czech Republic. rudolf@lfhk.cuni.cz
Andelová
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Cervinka
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D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053143:Caspase 2 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017879:Isothiocyanates; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D016159:Tumor Suppressor Protein p53; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; D053143:Caspase 2; C016766:sulforaphane