Preprint / Version 1

DIETARY PHYTOCHEMICALS INDUCE p53- AND CASPASE-INDEPENDENT CELL DEATH IN HUMAN NEUROBLASTOMA CELLS

Authors

  • Sangeetha Sukumari-Ramesh aDepartment of Neurosurgery, Georgia Health Sciences University, Augusta, GA 30912
  • J Bentley aDepartment of Neurosurgery, Georgia Health Sciences University, Augusta, GA 30912
  • Melissa Laird aDepartment of Neurosurgery, Georgia Health Sciences University, Augusta, GA 30912
  • Nagendra Singh bDepartment of Biochemistry, Georgia Health Sciences University, Augusta, GA 30912
  • John Vender aDepartment of Neurosurgery, Georgia Health Sciences University, Augusta, GA 30912
  • Krishnan Dhandapani aDepartment of Neurosurgery, Georgia Health Sciences University, Augusta, GA 30912

Keywords:

Ayurveda, Akt, pediatric cancer, nutrition, chemotherapy

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. Keywords: Ayurveda, Akt, pediatric cancer, nutrition, chemotherapy