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Evidence-Based Complementary and Alternative Medicine
Volume 2015, Article ID 394263, 9 pages
Research Article

Autophagic Cell Death by Poncirus trifoliata Rafin., a Traditional Oriental Medicine, in Human Oral Cancer HSC-4 Cells

1Department of Oral Pathology, School of Dentistry, Institute of Translational Dental Sciences, Pusan National University, Yangsan, Republic of Korea
2Department of Oral Anatomy, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
3Department of Herbology, College of Korean Medicine, Wonkwang University, Iksan, Republic of Korea
4Department of Preventive and Community Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
5Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea

Received 30 March 2015; Accepted 14 June 2015

Academic Editor: Waris Qidwai

Copyright © 2015 Hye-Yeon Han et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Poncirus trifoliata Rafin. has long been used as anti-inflammatory and antiallergic agent to treat gastrointestinal disorders and pulmonary diseases such as indigestion, constipation, chest fullness, chest pain, bronchitis, and sputum in Korea. P. trifoliata extract has recently been reported to possess anticancer properties; however, its mechanisms of action remain unclear. In this study, its antiproliferative effects and possible mechanisms were investigated in HSC-4 cells. The methanol extract of P. trifoliata (MEPT) significantly decreased the proliferation of HSC-4 cells (inhibitory concentration (IC)50 = 142.7 μg/mL) in a dose-dependent manner. While there were no significant changes observed upon cell cycle analysis and ANNEXIN V and 7-AAD double staining in the MEPT-treated groups, the intensity of acidic vesicular organelle (AVO) staining and microtubule-associated protein 1 light chain (LC) 3-II protein expression increased in response to MEPT treatment. Furthermore, 3-methyladenine (3-MA, autophagy inhibitor) effectively blocked the MEPT-induced cytotoxicity of HSC-4 cells and triggered the activation of p38 and extracellular signal-regulated kinases (ERK) proteins. Taken together, our results indicate that MEPT is a potent autophagy agonist in oral cancer cells with antitumor therapeutic potential that acts through the mitogen-activated protein kinase (MAPK) pathway.