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

Hye-Yeon Han; Mi Heon Ryu; Yonghae Son; Guemsan Lee; Seung-Hwa Jeong; Hyungwoo Kim

doi:10.4103/0973-1296.166056

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

Pharmacogn Mag. 2015 Oct;11(Suppl 2):S237-43. doi: 10.4103/0973-1296.166056.

Authors

Hye-Yeon Han¹, Mi Heon Ryu¹, Yonghae Son², Guemsan Lee³, Seung-Hwa Jeong⁴, Hyungwoo Kim²

Affiliations

¹ Department of Oral Pathology, School of Dentistry, Institute of translational Dental Sciences, Yangsan, South Korea.
² Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, South Korea.
³ Department of Herbology, College of Korean Medicine, Wonkwang, University, Iksan, South Korea.
⁴ Department of Preventive and Community Dentistry, School of Dentistry, Pusan National University, Yangsan, South Korea.

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.

Objectives: To evaluate the apoptosis-inducing activity of a P. trifoliata methanol extract (MEPT) and elucidate the molecular mechanisms.

Materials and 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).

Conclusion: 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.

Keywords: Apoptosis; Poncirus trifoliata; cancer therapy; tumor necrosis factor receptor.