title: Poncirus trifoliata Rafin. induces the apoptosis of triple-negative breast cancer cells via activation of the c-Jun NH(2)-terminal kinase and extracellular signal-regulated kinase pathways.
abstract: BACKGROUND
  Poncirus trifoliata Rafin. is a traditional medicine with known anti-inflammatory and anti-cancer properties. Traditionally, it is used to control chronic inflammation, allergy and gastrointestinal diseases such as digestive ulcers gastritis in China, Japan, and Korea.
  
  
  OBJECTIVE
  To evaluate the apoptosis-inducing activity of a P. trifoliata methanol extract (MEPT) and elucidate the molecular mechanisms.
  
  
  METHODS
  The anti-cancer effect of MEPT and its underlying mechanisms were investigated in breast cancer cells using 3,4,5-dimethyl N-methylthiazol-2-yl-2, 5-d-phenyl tetrazolium bromide assay, cell cycle analysis, and western blotting.
  
  
  RESULTS
  MEPT suppressed the proliferation of MDA-MB-231 cells with inhibition dose 50% value of 119.44 μg/mL at 24 h, which have features typical of triple-negative breast cancer cells. MEPT also altered the characteristic features of the MDA-MB-231 cells and increased the proportion of cells undergoing sub-G1 arrest. In addition, MEPT increased levels of caspase 8 and 3 in MDA-MB-231 cells, whereas caspase 9 was not detected. In addition, MEPT-induced tumor necrosis factor receptor (TNFR) and TNFR type 1-associated death domain (TRADD) protein and the activations of c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinases (ERK).
  
  
  CONCLUSIONS
  Our results indicate that MEPT has chemotherapeutic potential in triple-negative breast cancer and that at the molecular level its effects are derived from the activations of TNFR and of the mitogen-activated protein kinase pathway.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of translational Dental Sciences, Yangsan, South Korea.
authors.forename: Hye-Yeon
authors.initials: HY
authors.lastname: Han
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of translational Dental Sciences, Yangsan, South Korea.
authors.forename: Mi Heon
authors.initials: MH
authors.lastname: Ryu
authors.affiliation: Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, South Korea.
authors.forename: Yonghae
authors.initials: Y
authors.lastname: Son
authors.affiliation: Department of Herbology, College of Korean Medicine, Wonkwang, University, Iksan, South Korea.
authors.forename: Guemsan
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Preventive and Community Dentistry, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors.forename: Seung-Hwa
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, South Korea.
authors.forename: Hyungwoo
authors.initials: H
authors.lastname: Kim
keywords: Apoptosis; Poncirus trifoliata; cancer therapy; tumor necrosis factor receptor