TY - JOUR
T1 - Dietary phytochemicals induce p53- and caspase-independent cell death in human neuroblastoma cells
AU - Sukumari-Ramesh, Sangeetha
AU - Bentley, J. Nicole
AU - Laird, Melissa D.
AU - Singh, Nagendra
AU - Vender, John R.
AU - Dhandapani, Krishnan M.
N1 - Funding Information:
The authors’ research was supported in part by grants from the National Institutes of Health (NS065172) and the American Heart Association (BGIA2300135) to KMD, by a fellowship from the American Heart Association (2250690) to MDL, and by a grant from the A.R. Staulcup Foundation .
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
KW - Akt
KW - Ayurveda
KW - Chemotherapy
KW - Nutrition
KW - Pediatric cancer
UR - http://www.scopus.com/inward/record.url?scp=80053570990&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053570990&partnerID=8YFLogxK
U2 - 10.1016/j.ijdevneu.2011.06.002
DO - 10.1016/j.ijdevneu.2011.06.002
M3 - Article
C2 - 21704149
AN - SCOPUS:80053570990
SN - 0736-5748
VL - 29
SP - 701
EP - 710
JO - International Journal of Developmental Neuroscience
JF - International Journal of Developmental Neuroscience
IS - 7
ER -
