title: The molecular mechanism of action of aspirin, curcumin and sulforaphane             combinations in the chemoprevention of pancreatic cancer.
abstract: Pancreatic cancer ranks as the fourth most deadly form of cancer in the             United States with ~37,000 deaths each year. The present study evaluated the chemopreventive             potential of a combination of aspirin (ASP), curcumin (CUR) and sulforaphane (SFN)             in low doses to human pancreatic cancer cells, MIA PaCa-2 and Panc-1. Results             demonstrated that low doses of ASP (1 mM), CUR (10 µM) and SFN (5 µM) (ACS) combination             reduced cell viability by ~70% (P<0.001), and also induced cell apoptosis by             ~51% (P<0.001) accompanied by activation of caspase-3 and Poly(ADP-ribose)             polymerase (PARP) proteins. The NF-κB DNA binding activity was inhi-bited by ~45%             (P<0.01) and ~75% (P<0.001) in MIA PaCa-2 and Panc-1 cells, respectively.             Mechanistic studies revealed that ACS promoted increase expression of phospho             extracellular signal-regulated kinase 1/2 (P-ERK1/2), c-Jun, p38 MAPK and p53             proteins. Furthermore, the cells pretreated with U0126 (ERK1/2 inhibitor) partially             abolished the effect of ACS on cell viability. Data from this study demonstrate             that a low-dose ACS combination inhibits cell growth by inducing cell apoptosis,             and proposes sustained activation of the ERK1/2 signaling pathway as one of the             possible mechanisms.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors: Arvind
authors: A
authors: Thakkar
authors: Dhruvitkumar
authors: D
authors: Sutaria
authors: B Karthik
authors: BK
authors: Grandhi
authors: Jeffrey
authors: J
authors: Wang
authors: Sunil
authors: S
authors: Prabhu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D001241:Aspirin / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013454:Sulfoxides; D013861:Thiocyanates / Q000008:administration & dosage*
chemical_list: D004268:DNA-Binding Proteins; D017879:Isothiocyanates; D016328:NF-kappa B; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane; D003474:Curcumin; D001241:Aspirin
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