title: Moringa Oleifera aqueous leaf extract down-regulates nuclear factor-kappaB and increases cytotoxic effect of chemotherapy in pancreatic cancer cells.
abstract: BACKGROUND
  Fewer than 6% patients with adenocarcinoma of the pancreas live up to five years after diagnosis. Chemotherapy is currently the standard treatment, however, these tumors often develop drug resistance over time. Agents for increasing the cytotoxic effects of chemotherapy or reducing the cancer cells' chemo-resistance to the drugs are required to improve treatment outcome. Nuclear factor kappa B (NF-kB), a pro-inflammatory transcription factor, reportedly plays a significant role in the resistance of pancreatic cancer cells to apoptosis-based chemotherapy. This study investigated the effect of aqueous Moringa Oleifera leaf extract on cultured human pancreatic cancer cells - Panc-1, p34, and COLO 357, and whether it can potentiates the effect of cisplatin chemotherapy on these cells.
  
  
  METHODS
  The effect of Moringa Oleifera leaf extract alone and in combination with cisplatin on the survival of cultured human pancreatic cancer cells was evaluated by XTT-based colorimetric assay. The distribution of Panc-1 cells in the cell cycle following treatment with Moringa leaf extract was evaluated by flow cytometry, and evaluations of protein levels were via immunoblotting. Data of cell survival following combined treatments were analyzed with Calcusyn software.
  
  
  RESULTS
  Moringa Oleifera leaf extract inhibited the growth of all pancreatic cell lines tested. This effect was significant in all cells following exposure to ≥0.75 mg/ml of the extract. Exposure of Panc-1 cells to Moringa leaf extract induced an elevation in the sub-G1 cell population of the cell-cycle, and reduced the expression of p65, p-IkBα and IkBα proteins in crude cell extracts. Lastly, Moringa Oleifera leaf extract synergistically enhanced the cytotoxic effect of cisplatin on Panc-1 cells.
  
  
  CONCLUSIONS
  Moringa Oleifera leaf extract inhibits the growth of pancreatic cancer cells, the cells NF-κB signaling pathway, and increases the efficacy of chemotherapy in human pancreatic cancer cells.
authors: Laboratory of Herbal Medicine and Cancer Research, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors: Liron
authors: L
authors: Berkovich
authors: Gideon
authors: G
authors: Earon
authors: Ilan
authors: I
authors: Ron
authors: Adam
authors: A
authors: Rimmon
authors: Akiva
authors: A
authors: Vexler
authors: Shahar
authors: S
authors: Lev-Ari
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D029588:Moringa oleifera / Q000737:chemistry*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D014176:Protein Biosynthesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D010936:Plant Extracts; D002945:Cisplatin
references: Mutat Res. 1999 Apr 6;440(2):181-8
references: 10209341
references: Int J Mol Sci. 2011;12(9):6077-88
references: 22016645
references: HPB (Oxford). 2008;10(1):58-62
references: 18695761
references: J Gastrointest Surg. 2003 Jan;7(1):37-43; discussion 43
references: 12559183
references: Cancer Cell. 2004 Sep;6(3):203-8
references: 15380510
references: Pancreas. 2008 Apr;36(3):225-35
references: 18362834
references: J Tradit Chin Med. 2002 Dec;22(4):303-7
references: 16579100
references: Cancer Invest. 2007 Sep;25(6):411-8
references: 17882652
references: J Nat Prod. 2003 Jul;66(7):1022-37
references: 12880330
references: MedGenMed. 2007 Feb 06;9(1):26
references: 17435633
references: Mol Carcinog. 2005 Sep;44(1):51-9
references: 16044419
references: Integr Cancer Ther. 2009 Mar;8(1):29-36
references: 19174505
references: J Biol Chem. 2004 May 28;279(22):23477-85
references: 15026414
references: Recent Pat Biotechnol. 2007;1(2):139-50
references: 19075837
references: JOP. 2011 Mar 09;12(2):96-100
references: 21386629
references: Anticancer Agents Med Chem. 2011 Jun;11(5):418-26
references: 21521155
references: Nat Immunol. 2002 Mar;3(3):221-7
references: 11875461
references: Food Chem Toxicol. 2011 Jun;49(6):1270-5
references: 21385597
references: J Ethnopharmacol. 2012 Jan 31;139(2):330-6
references: 22138517
references: Clin Cancer Res. 2007 Feb 15;13(4):1076-82
references: 17317814