title: Autophagic Cell Death by Poncirus trifoliata Rafin., a Traditional Oriental Medicine, in Human Oral Cancer HSC-4 Cells.
abstract: 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.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Translational Dental Sciences, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Hye-Yeon
authors.initials: HY
authors.lastname: Han
authors.affiliation: Department of Oral Anatomy, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Bong-Soo
authors.initials: BS
authors.lastname: Park
authors.affiliation: Department of Herbology, College of Korean Medicine, Wonkwang University, Iksan, Republic of Korea.
authors.forename: Guem San
authors.initials: GS
authors.lastname: Lee
authors.affiliation: Department of Preventive and Community Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Seung-Hwa
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Hyungwoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Translational Dental Sciences, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Mi Heon
authors.initials: MH
authors.lastname: Ryu