title: Dietary phytochemicals induce p53- and caspase-independent cell death in human neuroblastoma cells.
abstract: Neuroblastoma (NB) is the most prevalent pediatric solid tumor and a leading cause of cancer-related death in children. In the present study, a novel cytotoxic role for the dietary compounds, curcumin, andrographolide, wedelolactone, dibenzoylmethane, and tanshinone IIA was identified in human S-type NB cells, SK-N-AS and SK-N-BE(2). Mechanistically, cell death appeared apoptotic by flow cytometry; however, these effects proceeded independently from both caspase-3 and p53 activation, as assessed by both genetic (shRNA) and pharmacological approaches. Notably, cell death induced by both curcumin and andrographolide was associated with decreased NFκB activity and a reduction in Bcl-2 and Bcl-xL expression. Finally, curcumin and andrographolide increased cytotoxicity following co-treatment with either cisplatin or doxorubicin, two chemotherapeutic agents widely used in the clinical management of NB. Coupled with the documented safety in humans, dietary compounds may represent a potential adjunct therapy for NB.
authors.affiliation: Department of Neurosurgery, Georgia Health Sciences University, Augusta, GA 30912, United States.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Sukumari-Ramesh
authors.forename: J Nicole
authors.initials: JN
authors.lastname: Bentley
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Laird
authors.forename: Nagendra
authors.initials: N
authors.lastname: Singh
authors.forename: John R
authors.initials: JR
authors.lastname: Vender
authors.forename: Krishnan M
authors.initials: KM
authors.lastname: Dhandapani
mesh_terms: D045784:Abietanes / Q000008:administration & dosage / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000008:administration & dosage / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003374:Coumarins / Q000008:administration & dosage / Q000494:pharmacology; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology; D004032:Diet; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009447:Neuroblastoma / Q000178:diet therapy / Q000188:drug therapy / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D045784:Abietanes; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D047188:Chalcones; D002867:Chromones; D003374:Coumarins; D004224:Diterpenes; D009025:Morpholines; D016328:NF-kappa B; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; C021751:tanshinone; C051122:wedelolactone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C030419:andrographolide; C061481:dibenzoylmethane; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D003474:Curcumin