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Dietary phytochemicals induce p53‐ and caspase‐independent cell death in human neuroblastoma cells
Author(s) -
SukumariRamesh Sangeetha,
Bentley J. Nicole,
Laird Melissa D.,
Singh Nagendra,
Vender John R.,
Dhandapani Krishnan M.
Publication year - 2011
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2011.06.002
Subject(s) - apoptosis , neuroblastoma , programmed cell death , caspase , caspase 3 , cancer research , microbiology and biotechnology , chemistry , biology , biochemistry , cell culture , genetics
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.