Apple and hop-polyphenols inhibit porphyromonas gingivalis-mediated precursor of matrix metalloproteinase-9 activation and invasion of oral squamous cell carcinoma cells

Hiroaki Inaba, Motoyuki Tagashira, Tomomasa Kanda, Yukitaka Murakami, Atsuo Amano, Michiyo Nakano

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Recent epidemiologic studies have revealed a significant association between periodontitis and oral squamous cell carcinoma (OSCC). Furthermore, periodontitis ismarkedly associated with orodigestive cancer mortality, whereas Porphyromonas gingivalis (Pg) infection has been identified as a specific and potentially independent microbial factor related to increased risk of orodigestive cancer death. The authors previously reported that Pg induced the precursor form of matrix metalloproteinase-9 (proMMP-9) production via proteinaseactivated receptor (PAR)-related pathways, after which proMMP-9 was activated by gingipains to enhance cellular invasion of SAS cells. In the present study, effects of selected polyphenols as inhibitors of cellular invasion caused by Pg gingipains in SAS cells are examined. Methods: OSCC cells were infected with Pg strains including gingipain mutants. To evaluate effects of inhibitors: 1) apple polyphenol (AP); 2) hop bract polyphenol (HBP); 3) high-molecular-weight fractions of HBP (HMW-HBP); 4) low-molecular-weight fractions of HBP (LMW-HBP); 5) epigallocatechin gallate (EGCg); 6) KYT-1 (Arg-gingipain inhibitor); and KYT-36 (Lys-gingipain inhibitor) in combination are used. PAR2 and PAR4 mRNA expressions are examined using real-time reverse transcription polymerase chain reaction, and signaling pathways are evaluated by western blotting analysis. Results: KYT-1/KYT-36, AP, HBP, and HMW-HBP significantly inhibited PAR2 and PAR4 mRNA expressions, proMMP-9 activation, and cellular invasion. Furthermore, AP, HBP, and HMW-HBP reduced activation of heat shock protein 27 and Ets1 and nuclear translocation of nuclear factor-kappa B, whereas EGCg and LMW-HBP did not. Conclusion: These results suggest that AP, HBP, HMW-HBP are potent inhibitors of proMMP-9 activation and cellular invasion mediated with Pg in OSCC cells.

Original languageEnglish
Pages (from-to)1103-1111
Number of pages9
JournalJournal of Periodontology
Volume87
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

Humulus
Porphyromonas gingivalis
Matrix Metalloproteinase 9
Malus
Polyphenols
Squamous Cell Carcinoma
Molecular Weight
Periodontitis
HSP27 Heat-Shock Proteins
NF-kappa B
RNA Precursors
Reverse Transcription
Epidemiologic Studies
Neoplasms
Western Blotting

Keywords

  • Carcinoma
  • Cell biology
  • Matrix metalloproteinases
  • Microbiology
  • Polyphenols
  • Porphyromonas gingivalis

ASJC Scopus subject areas

  • Periodontics

Cite this

Apple and hop-polyphenols inhibit porphyromonas gingivalis-mediated precursor of matrix metalloproteinase-9 activation and invasion of oral squamous cell carcinoma cells. / Inaba, Hiroaki; Tagashira, Motoyuki; Kanda, Tomomasa; Murakami, Yukitaka; Amano, Atsuo; Nakano, Michiyo.

In: Journal of Periodontology, Vol. 87, No. 9, 01.09.2016, p. 1103-1111.

Research output: Contribution to journalArticle

@article{0e5de37c669f449790773350a963cc85,
title = "Apple and hop-polyphenols inhibit porphyromonas gingivalis-mediated precursor of matrix metalloproteinase-9 activation and invasion of oral squamous cell carcinoma cells",
abstract = "Background: Recent epidemiologic studies have revealed a significant association between periodontitis and oral squamous cell carcinoma (OSCC). Furthermore, periodontitis ismarkedly associated with orodigestive cancer mortality, whereas Porphyromonas gingivalis (Pg) infection has been identified as a specific and potentially independent microbial factor related to increased risk of orodigestive cancer death. The authors previously reported that Pg induced the precursor form of matrix metalloproteinase-9 (proMMP-9) production via proteinaseactivated receptor (PAR)-related pathways, after which proMMP-9 was activated by gingipains to enhance cellular invasion of SAS cells. In the present study, effects of selected polyphenols as inhibitors of cellular invasion caused by Pg gingipains in SAS cells are examined. Methods: OSCC cells were infected with Pg strains including gingipain mutants. To evaluate effects of inhibitors: 1) apple polyphenol (AP); 2) hop bract polyphenol (HBP); 3) high-molecular-weight fractions of HBP (HMW-HBP); 4) low-molecular-weight fractions of HBP (LMW-HBP); 5) epigallocatechin gallate (EGCg); 6) KYT-1 (Arg-gingipain inhibitor); and KYT-36 (Lys-gingipain inhibitor) in combination are used. PAR2 and PAR4 mRNA expressions are examined using real-time reverse transcription polymerase chain reaction, and signaling pathways are evaluated by western blotting analysis. Results: KYT-1/KYT-36, AP, HBP, and HMW-HBP significantly inhibited PAR2 and PAR4 mRNA expressions, proMMP-9 activation, and cellular invasion. Furthermore, AP, HBP, and HMW-HBP reduced activation of heat shock protein 27 and Ets1 and nuclear translocation of nuclear factor-kappa B, whereas EGCg and LMW-HBP did not. Conclusion: These results suggest that AP, HBP, HMW-HBP are potent inhibitors of proMMP-9 activation and cellular invasion mediated with Pg in OSCC cells.",
keywords = "Carcinoma, Cell biology, Matrix metalloproteinases, Microbiology, Polyphenols, Porphyromonas gingivalis",
author = "Hiroaki Inaba and Motoyuki Tagashira and Tomomasa Kanda and Yukitaka Murakami and Atsuo Amano and Michiyo Nakano",
year = "2016",
month = "9",
day = "1",
doi = "10.1902/jop.2016.160047",
language = "English",
volume = "87",
pages = "1103--1111",
journal = "Journal of Periodontology",
issn = "0022-3492",
publisher = "American Academy of Periodontology",
number = "9",

}

TY - JOUR

T1 - Apple and hop-polyphenols inhibit porphyromonas gingivalis-mediated precursor of matrix metalloproteinase-9 activation and invasion of oral squamous cell carcinoma cells

AU - Inaba, Hiroaki

AU - Tagashira, Motoyuki

AU - Kanda, Tomomasa

AU - Murakami, Yukitaka

AU - Amano, Atsuo

AU - Nakano, Michiyo

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background: Recent epidemiologic studies have revealed a significant association between periodontitis and oral squamous cell carcinoma (OSCC). Furthermore, periodontitis ismarkedly associated with orodigestive cancer mortality, whereas Porphyromonas gingivalis (Pg) infection has been identified as a specific and potentially independent microbial factor related to increased risk of orodigestive cancer death. The authors previously reported that Pg induced the precursor form of matrix metalloproteinase-9 (proMMP-9) production via proteinaseactivated receptor (PAR)-related pathways, after which proMMP-9 was activated by gingipains to enhance cellular invasion of SAS cells. In the present study, effects of selected polyphenols as inhibitors of cellular invasion caused by Pg gingipains in SAS cells are examined. Methods: OSCC cells were infected with Pg strains including gingipain mutants. To evaluate effects of inhibitors: 1) apple polyphenol (AP); 2) hop bract polyphenol (HBP); 3) high-molecular-weight fractions of HBP (HMW-HBP); 4) low-molecular-weight fractions of HBP (LMW-HBP); 5) epigallocatechin gallate (EGCg); 6) KYT-1 (Arg-gingipain inhibitor); and KYT-36 (Lys-gingipain inhibitor) in combination are used. PAR2 and PAR4 mRNA expressions are examined using real-time reverse transcription polymerase chain reaction, and signaling pathways are evaluated by western blotting analysis. Results: KYT-1/KYT-36, AP, HBP, and HMW-HBP significantly inhibited PAR2 and PAR4 mRNA expressions, proMMP-9 activation, and cellular invasion. Furthermore, AP, HBP, and HMW-HBP reduced activation of heat shock protein 27 and Ets1 and nuclear translocation of nuclear factor-kappa B, whereas EGCg and LMW-HBP did not. Conclusion: These results suggest that AP, HBP, HMW-HBP are potent inhibitors of proMMP-9 activation and cellular invasion mediated with Pg in OSCC cells.

AB - Background: Recent epidemiologic studies have revealed a significant association between periodontitis and oral squamous cell carcinoma (OSCC). Furthermore, periodontitis ismarkedly associated with orodigestive cancer mortality, whereas Porphyromonas gingivalis (Pg) infection has been identified as a specific and potentially independent microbial factor related to increased risk of orodigestive cancer death. The authors previously reported that Pg induced the precursor form of matrix metalloproteinase-9 (proMMP-9) production via proteinaseactivated receptor (PAR)-related pathways, after which proMMP-9 was activated by gingipains to enhance cellular invasion of SAS cells. In the present study, effects of selected polyphenols as inhibitors of cellular invasion caused by Pg gingipains in SAS cells are examined. Methods: OSCC cells were infected with Pg strains including gingipain mutants. To evaluate effects of inhibitors: 1) apple polyphenol (AP); 2) hop bract polyphenol (HBP); 3) high-molecular-weight fractions of HBP (HMW-HBP); 4) low-molecular-weight fractions of HBP (LMW-HBP); 5) epigallocatechin gallate (EGCg); 6) KYT-1 (Arg-gingipain inhibitor); and KYT-36 (Lys-gingipain inhibitor) in combination are used. PAR2 and PAR4 mRNA expressions are examined using real-time reverse transcription polymerase chain reaction, and signaling pathways are evaluated by western blotting analysis. Results: KYT-1/KYT-36, AP, HBP, and HMW-HBP significantly inhibited PAR2 and PAR4 mRNA expressions, proMMP-9 activation, and cellular invasion. Furthermore, AP, HBP, and HMW-HBP reduced activation of heat shock protein 27 and Ets1 and nuclear translocation of nuclear factor-kappa B, whereas EGCg and LMW-HBP did not. Conclusion: These results suggest that AP, HBP, HMW-HBP are potent inhibitors of proMMP-9 activation and cellular invasion mediated with Pg in OSCC cells.

KW - Carcinoma

KW - Cell biology

KW - Matrix metalloproteinases

KW - Microbiology

KW - Polyphenols

KW - Porphyromonas gingivalis

UR - http://www.scopus.com/inward/record.url?scp=84985905822&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84985905822&partnerID=8YFLogxK

U2 - 10.1902/jop.2016.160047

DO - 10.1902/jop.2016.160047

M3 - Article

C2 - 27177287

AN - SCOPUS:84985905822

VL - 87

SP - 1103

EP - 1111

JO - Journal of Periodontology

JF - Journal of Periodontology

SN - 0022-3492

IS - 9

ER -