The flavonoid p-hydroxycinnamic acid exhibits anticancer effects in human pancreatic cancer MIA PaCa-2 cells in vitro: Comparison with gemcitabine

Abstract

Pancreatic cancer is a highly aggressive malignancy with a notoriously dismal prognosis. A major contributor to this poor clinical outcome is pancreatic cancer's prominent chemoresistance. The present study was undertaken to determine whether the flavonoid p-hydroxycinnamic acid (HCA), which is a botanical factor, possesses anticancer effects on cloned human pancreatic cancer MIA PaCa-2 cells that possess resistance to radiation therapy in vitro. Proliferation of MIA PaCa-2 cells was suppressed after culture with HCA (10-1,000 nM). Such an effect was also noted in human pancreatic cancer Pt45P1 cells. In the MIA PaCa-2 cells, HCA induced G1 and G2/M phase cell cycle arrest in the cells. The suppressive effects of HCA on proliferation were suggested to be mediated through the inhibition of various signaling pathways related to nuclear factor-κB (NF-κB), extracellular signal-regulated kinase (ERK), protein kinase C, phosphatidylinositol 3-kinase (PI3K) or nuclear transcription activity. Moreover, HCA was found to stimulate cell death in the MIA PaCa-2 and Pt45P1 cells in vitro. The anticancer effects of HCA on MIA PaCa-2 cells were exhibited at a lower concentration than gemcitabine, a potent cancer drug. The flavonoid HCA may be a useful tool in the therapy of human pancreatic cancer in vivo.