title: Helioxanthin suppresses the cross talk of COX-2/PGE2 and EGFR/ERK pathway to inhibit Arecoline-induced Oral Cancer Cell (T28) proliferation and blocks tumor growth in xenografted nude mice.
abstract: Helioxanthin, an active compound from Taiwania cryptomerioides Hayata, has been shown to have various biological activities. However, their anticancer effect in oral squamous cell carcinoma has not been well established yet. Helioxanthin inhibited the proliferation of oral squamous cell carcinoma cells in a dose-dependent manner by inducing G2/M phase arrest. Similarly, helioxanthin inhibited cyclooxygenase-2, (COX-2), phosphorylated EGFR, and extracellular-signal-regulated kinases (ERK) protein level and further reduced the nuclear accumulation of phosphorylated epidermal growth factor receptor (pEGFR) and activator protein-1(AP-1) family protein, c-fos. Moreover, helioxanthin at the dose of 20 and 30 mg kg-1for 15 days reduced the tumor growth in animal model. This study demonstrated that Helioxanthin exerts its anticancer activity against oral cancer cells by downregulating EGFR/ERK/c-fos signaling pathway to inhibit COX-2 level and by activating cyclin-dependent kinase inhibitor (p27) to further induce G2/M cell cycle arrest. This helioxanthin may serve as a novel candidate for oral cancer prevention. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2045-2056, 2016.
authors.affiliation: Department of pathology, Changhua Christian Hospital, Changhua, Taiwan.|Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Bharath Kumar
authors.initials: BK
authors.lastname: Velmurugan
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Hau-Hsueh
authors.initials: HH
authors.lastname: Hsien
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: You-Liang
authors.initials: YL
authors.lastname: Hsieh
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: 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: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
authors.affiliation: Department of Biotechnology, Bharathiar University, Coimbatore-641 046, India.
authors.forename: Vijaya Padma
authors.initials: VP
authors.lastname: Viswanadha
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.|Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001115:Arecoline; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D064593:Heterografts; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D020935:MAP Kinase Signaling System; D008297:Male; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017705:Lignans; D018808:Transcription Factor AP-1; C505802:helioxanthin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D001115:Arecoline; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone
keywords: COX-2; EGFR; T28; helioxanthin; oral cancer cells; p27