The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer

Pancreatic cancer ranks as the fourth most deadly form of cancer in theUnited States with ~37,000 deaths each year. The present study evaluated the chemopreventivepotential 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. Resultsdemonstrated that low doses of ASP (1 mM), CUR (10 µM) and SFN (5 µM) (ACS) combinationreduced 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 phosphoextracellular signal-regulated kinase 1/2 (P-ERK1/2), c-Jun, p38 MAPK and p53proteins. Furthermore, the cells pretreated with U0126 (ERK1/2 inhibitor) partiallyabolished the effect of ACS on cell viability. Data from this study demonstratethat 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 thepossible mechanisms.