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

Jin Hyoung Cho, Young Joo Jeon, Seon Min Park, Jae Cheon Shin, Tae Hoon Lee, Seunggon Jung, Hongju Park, Joohyun Ryu, Hanyong Chen, Zigang Dong, Jung Hyun Shim, Jung Il Chae

Research output: Contribution to journalArticle

21 Scopus citations

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. Invitro and invivo 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.

Original languageEnglish (US)
Pages (from-to)274-284
Number of pages11
JournalBiomaterials
Volume53
DOIs
StatePublished - Jun 1 2015

Keywords

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

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