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  • Multifunctional effects of honokiol as an anti-inflammatory and anti-cancer drug in human oral squamous cancer cells and xenograft.

    (전북대: 조진형, 채정일*)

  • 출처
    Biomaterials
  • 등재일
    2015 Jun
  • 저널이슈번호
    53:274-84
  • 내용

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    [Abstract]

    The aim of this study was to investigate anti-inflammatory and anti-cancer effects of honokiol (HK) in two oral squamous cancer cell carcinoma (OSCC) cell lines, HN22 and HSC4, through the regulation of inducible nitric oxide synthase (iNOS) and endoplasmic reticulum resident protein 44 (ERp44). Griess assay, zymography, and quantitative PCR were performed to study iNOS expression and subsequent nitric oxide (NO) production in OSCC cell lines. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic analysis was used to elucidate the proteins associated with ER stress and cellular cytotoxic response induced by HK. Pull-down assay and molecular modeling were performed to better understand how HK interacts with ERp44. In vitro and in vivo experiments in which ERp44 expression was knocked down were performed to better understand the effects of ERp44 on a cellular level and anti-cancer effects of HK. Expression levels of iNOS and subsequent NO secretion were reduced in OSCC cell lines treated with HK. ERp44 was significantly decreased in OSCC cell lines by HK treatment. HK directly bound to ERp44, and ERp44 knock-down significantly inhibited oral cancer cell proliferation and colony formation. Moreover, HK treatment effectively inhibited tumor growth and ERp44 levels in BALB/c nude mice bearing HN22 cell xenografts. Our findings suggest that HK inhibited inflammation and induced apoptosis by suppressing both iNOS/NO and ERp44 expression in HN22 and HSC4 cells and xenograft tumors, and thus could be a potent anti-inflammatory and anti-cancer drug candidate for human oral cancer treatment.

     

    Copyright © 2015 Elsevier Ltd. All rights reserved.

     

    [Author information]

    Cho JH1, Jeon YJ1, Park SM2, Shin JC2, Lee TH3, Jung S4, Park H5, Ryu J6, Chen H6, Dong Z6, Shim JH7, Chae JI8.

    1 Department of Oral Pharmacology, School of Dentistry and Institute of Dental Bioscience, BK21 Plus, Chonbuk National University, Jeonju 651-756, Republic of Korea.

    2 Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk, Republic of Korea.

    3 Department of Oral Biochemistry, Dental Science Research Institute and the BK21 Project, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.

    4 Department of Oral and Maxillofacial Surgery, Chonnam National University Hwasun Hospital, Gwangju, Republic of Korea.

    5 Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.

    6 The Hormel Institute, University of Minnesota, Austin, MN, USA.

    7 Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam 534-729, Republic of Korea. Electronic address: s1004jh@gmail.com.

    8 Department of Oral Pharmacology, School of Dentistry and Institute of Dental Bioscience, BK21 Plus, Chonbuk National University, Jeonju 651-756, Republic of Korea. Electronic address: jichae@jbnu.ac.kr. 

  • 키워드
    Apoptosis; Endoplasmic reticulum resident protein 44; Honokiol; Oral squamous cell carcinoma; Proteomics; Xenograft
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