title: Impact of curcumin, raspberry extract, and neem leaf extract on rel protein-regulated cell death/radiosensitization in pancreatic cancer cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Radiation Oncology, University of Oklahoma Health Sciences Center, 825 NE 10th St, Oklahoma City, OK 73104, USA. naravind@ouhsc.edu
authors.forename: Jamunarani
authors.initials: J
authors.lastname: Veeraraghavan
authors.forename: Mohan
authors.initials: M
authors.lastname: Natarajan
authors.forename: Pallavi
authors.initials: P
authors.lastname: Lagisetty
authors.forename: Vibhudutta
authors.initials: V
authors.lastname: Awasthi
authors.forename: Terence S
authors.initials: TS
authors.lastname: Herman
authors.forename: Natarajan
authors.initials: N
authors.lastname: Aravindan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D031601:Azadirachta; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005638:Fruit; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D027824:Rosaceae; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020672:I-kappa B Proteins; D052002:NF-kappa B p50 Subunit; C000606204:NFKBIA protein, human; D010936:Plant Extracts; C498143:RELA protein, human; D011838:Radiation-Sensitizing Agents; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA; D003474:Curcumin