Neem leaf extract induces radiosensitization in human neuroblastoma xenograft through modulation of apoptotic pathway

Jamunarani Veeraraghavan, Sheeja Aravindan, Mohan Natarajan, Vibhudutta Awasthi, Terence S. Herman, Natarajan Aravindan

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)161-170
Number of pages10
JournalAnticancer Research
Volume31
Issue number1
StatePublished - Jan 1 2011

Keywords

  • Apoptosis
  • Neem leaf extract
  • Neuroblastoma
  • Radiotherapy
  • Transcriptional response

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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