Dietary phytochemicals induce p53- and caspase-independent cell death in human neuroblastoma cells.

Sangeetha Sukumari-Ramesh, J Nicole Bentley, Melissa D Laird, Nagendra Singh, John R Vender, Krishnan M Dhandapani

Index: Int. J. Dev. Neurosci. 29(7) , 701-10, (2011)

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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.Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.