TY - JOUR
T1 - Neem leaf extract induces radiosensitization in human neuroblastoma xenograft through modulation of apoptotic pathway
AU - Veeraraghavan, Jamunarani
AU - Aravindan, Sheeja
AU - Natarajan, Mohan
AU - Awasthi, Vibhudutta
AU - Herman, Terence S.
AU - Aravindan, Natarajan
PY - 2011/1
Y1 - 2011/1
N2 - Induction of apoptosis is directly correlated with the biological effectiveness of ionizing radiation (IR). Accordingly, we investigated the efficacy ofneem leaf extract (NLE) on IR-associated apoptotic transcriptional modulation and cell death in neuroblastoma (NB). Materials and Methods: NB xenografts exposed to single dose (SDR, 10 Gy) or fractionated (FIR, 2 Gy/dx5d) with or without NLE were examined for transcriptional activation of 84 apoptotic pathway genes using quantitative polymerase chain reaction. Apoptosis was measured using TdT nick-end labeling. Results: FIR induced 55 and suppressed 10 genes, while SDR induced 49 and suppressed 5 genes. Of these, 46 and 4 genes were commonly up/down-regulated after FIR and SDR. NLE inhibited IR-induced NAIP, BIRC6, BIRC8, NOL3 and enhanced BAK1, BAX, BCL10, CASP1, CASP10 CARD8 and CRADD. Furthermore, NLE conferred FIR- and SDR-induced cell death. Conclusion: These data imply that NLE may exert radiosensitization by activating pro-apoptotic signaling and negating survival signaling and may thus potentiate radiotherapy in NB.
AB - Induction of apoptosis is directly correlated with the biological effectiveness of ionizing radiation (IR). Accordingly, we investigated the efficacy ofneem leaf extract (NLE) on IR-associated apoptotic transcriptional modulation and cell death in neuroblastoma (NB). Materials and Methods: NB xenografts exposed to single dose (SDR, 10 Gy) or fractionated (FIR, 2 Gy/dx5d) with or without NLE were examined for transcriptional activation of 84 apoptotic pathway genes using quantitative polymerase chain reaction. Apoptosis was measured using TdT nick-end labeling. Results: FIR induced 55 and suppressed 10 genes, while SDR induced 49 and suppressed 5 genes. Of these, 46 and 4 genes were commonly up/down-regulated after FIR and SDR. NLE inhibited IR-induced NAIP, BIRC6, BIRC8, NOL3 and enhanced BAK1, BAX, BCL10, CASP1, CASP10 CARD8 and CRADD. Furthermore, NLE conferred FIR- and SDR-induced cell death. Conclusion: These data imply that NLE may exert radiosensitization by activating pro-apoptotic signaling and negating survival signaling and may thus potentiate radiotherapy in NB.
KW - Apoptosis
KW - Neem leaf extract
KW - Neuroblastoma
KW - Radiotherapy
KW - Transcriptional response
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UR - http://www.scopus.com/inward/citedby.url?scp=79851491514&partnerID=8YFLogxK
M3 - Article
C2 - 21273594
AN - SCOPUS:79851491514
SN - 0250-7005
VL - 31
SP - 161
EP - 170
JO - Anticancer Research
JF - Anticancer Research
IS - 1
ER -