title: DAPK1 modulates a curcumin-induced G2/M arrest and apoptosis by regulating STAT3, NF-κB, and caspase-3 activation.
abstract: Curcumin, an active polyphenol extracted from the perennial herb Curcuma longa, controls various molecules involved in tumor cell death. In this study, we found that the tumor suppressor death-associated protein kinase 1 (DAPK1) plays a vital role in the anti-carcinogenic effects of curcumin. We found that curcumin increased DAPK1 expression at the mRNA and protein levels in U251 cells, and that the siRNA-mediated knockdown of DAPK1 attenuated the curcumin-induced inhibition of STAT3 and NF-κB. Moreover, DAPK1 suppression diminished curcumin-induced caspase-3 activation. In addition, we confirmed that DAPK1 was required for a curcumin-induced G2/M cell cycle arrest and apoptosis. Thus, DAPK1 is involved in curcumin-mediated death pathways. Our data suggest novel mechanisms for curcumin in cancer therapy.
authors.affiliation: Affiliated Bayi Brain Hospital, Bayi Clinical College, Southern Medical University, Beijing, PR China.
authors.forename: Bingshan
authors.initials: B
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.forename: Ruxiang
authors.initials: R
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000172:deficiency / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000378:metabolism / Q000494:pharmacology*; D064550:Death-Associated Protein Kinases; D016195:G2 Phase / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D003474:Curcumin