Impact of curcumin, raspberry extract, and neem leaf extract on rel protein-regulated cell death/radiosensitization in pancreatic cancer cells

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

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Objectives: Nuclear factor κB (NF-κB) plays an intrinsic role in promoting growth, angiogenesis, and metastasis in pancreatic cancer (PC) and serves as a mechanism underlying therapeutic resistance. Accordingly, we investigated the efficacy of bioactive phytochemicals in inhibiting radiotherapy (RT)-induced NF-κB activity, signaling, and NF-κB-dependent regulation of cell death. Methods: Panc-1, BxPC-3, and MIA PaCa-2 cells exposed to 10 Gy (single high dose [SDR]) or 2 Gy/d for 5 days (fractionated radiation [FIR]) with or without curcumin (CUR), neem leaf extract (NLE), or black raspberry extract (RSE) were analyzed. Results: Radiotherapy profoundly induced NF-κB-DNA-binding activity with relatively robust activation after FIR. Curcumin, NLE, and RSE significantly inhibited both constitutive and RT-induced NF-κB. Furthermore, quantitative polymerase chain reaction profiling of 88 NF-κB pathway molecules demonstrated that CUR, NLE, and RSE comprehensively, yet differentially inhibited FIR/SDR-induced genes. Functionally, CUR, NLE, and RSE markedly conferred RT-inhibited cell viability/survival, robustly activated caspase-3/7 activity, and subsequent cell death. More importantly, NF-κB overexpression and silencing studies demonstrate that these compounds potentiate RT-induced cell death by targeting RT-induced NF-κB. Conclusions: These data strongly imply that CUR, NLE, and RSE may serve as effective "deliverables" to potentiate RT in PC cure and further throw light that these phytochemicals-induced cell killing may involve selective regulation of RT-induced NF-κB.

Original languageEnglish (US)
Pages (from-to)1107-1119
Number of pages13
JournalPancreas
Volume40
Issue number7
DOIs
StatePublished - Oct 1 2011

Keywords

  • NF-κB
  • curcumin
  • neem
  • pancreatic cancer
  • radiosensitization
  • raspberry

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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