title: 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.
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA 30322, USA.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Tempaku, Nagoya 468‑8503, Japan.
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Murata
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA 30322, USA.
authors.forename: Bassel F
authors.initials: BF
authors.lastname: El-Rayes
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA 30322, USA.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Shoji
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects; D003373:Coumaric Acids / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids / Q000008:administration & dosage; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D000093542:Gemcitabine
chemical_list: D003373:Coumaric Acids; D005419:Flavonoids; D003841:Deoxycytidine; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000093542:Gemcitabine