title: Taiwanin C selectively inhibits arecoline and 4-NQO-induced oral cancer cell proliferation via ERK1/2 inactivation.
abstract: Arecoline, the most abundant alkaloid in betel nut is known to promote abnormal proliferation of epithelial cells by enhancing epidermal growth factor receptor (EGFR) activation and cyclooxygenase-2 (COX2) expression. Taiwanin C, a naturally occurring lignan extracted from Taiwania cryptomerioides, has been found to be a potential inhibitor of COX2 expression. Based on the MTT assay results, taiwanin C was found to be effective in inhibiting the tumorous T28 cell than the non-tumorous N28 cells. The modulations in the expression of relevant proteins were determined to understand the mechanism induced by taiwanin C to inhibit T28 cell proliferation. The levels of activated EGFR and COX2 were found to be abnormally high in the T28 oral cancer cells. However, taiwanin C was found to inhibit the activation of EGFR and regulated other related downstream proteins and thereby inhibited the T28 cell proliferation. In conclusion the results indicate that taiwanin C suppresses COX2-EGFR and enhances P27 pathways to suppress arecoline induced oral cancer cell proliferation via ERK1/2 inactivation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 62-69, 2017.
authors.affiliation: Emergency Department, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Kuan-Ho
authors.initials: KH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Marthandam Asokan
authors.initials: MA
authors.lastname: Shibu
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Yueh-Chiu
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan.|Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
authors.affiliation: Division of Colorectal Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Armed Force Taichung General Hospital, Taichung, Taiwan.
authors.forename: Chuan-Chou
authors.initials: CC
authors.lastname: Tu
authors.affiliation: Department of Biotechnology, Bharathiar University, Tamil Nadu, Coimbatore, India.
authors.forename: Vijaya Padma
authors.initials: VP
authors.lastname: Viswanadha
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.|School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001115:Arecoline / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D017705:Lignans / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009062:Mouth Neoplasms / Q000473:pathology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D017705:Lignans; C467766:taiwanin C; D001115:Arecoline; D015112:4-Nitroquinoline-1-oxide; C541485:EGFR protein, mouse; D066246:ErbB Receptors
keywords: Taiwania cryptomerioides; arecoline; oral cancer; taiwanin C