The Molecular Mechanism of Action of Aspirin, Curcumin and Sulforaphane Combinations in the Chemoprevention of Pancreatic Cancer

Oncol Rep. 2013 Apr;29(4):1671-7. doi: 10.3892/or.2013.2276. Epub 2013 Feb 5.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols
  • Aspirin / administration & dosage*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Curcumin / administration & dosage*
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Isothiocyanates
  • MAP Kinase Signaling System / drug effects
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Thiocyanates / administration & dosage*

Substances

  • DNA-Binding Proteins
  • Isothiocyanates
  • NF-kappa B
  • Thiocyanates
  • sulforafan
  • Curcumin
  • Aspirin