title: Porphyromonas gingivalis-induced autophagy suppresses cell proliferation through G1 arrest in oral cancer cells.
abstract: OBJECTIVE
  We investigated the response of oral cancer cells to intracellular invasion of Porphyromonas gingivalis to define changes in the biological characteristics of oral cancer cells evoked by the presence of oral pathogenic bacteria within a tumour microenvironment.
  
  
  METHODS
  The proliferative activity, cell cycle, and autophagic response were evaluated in oral cancer cells infected with P. gingivalis 381. ROS generation was detected in these cells by DCFDA assay, and its role in the responses of oral cancer cells to P. gingivalis infection was further investigated.
  
  
  RESULTS
  P. gingivalis inhibited proliferation of oral cancer cells by inducing G1 cell cycle arrest, but had no effect on apoptosis. Following infection with P. gingivalis, the expression of cyclin D1 and cdk4 was decreased in oral cancer cells, whereas p21, a Cdk inhibitor, was upregulated, in comparison with non-infected controls. Autophagy was prominently enhanced in these infected cells, presumably contributing to the suppressed proliferation. Further experiments revealed that such autophagic response was activated by the formation of reactive oxygen species, as evidenced by the lack of autophagic response and cell proliferation upon removal of reactive oxygen species.
  
  
  CONCLUSIONS
  These findings provide a novel insight into the mechanism by which cancer cells are influenced by tumour microenvironment including oral bacteria.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan, 626-870, South Korea.
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Cho
authors.affiliation: Department of Oral Pathology, School of Dentistry, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan, 626-870, South Korea.
authors.forename: Shin Wook
authors.initials: SW
authors.lastname: Wee
authors.affiliation: Department of Oral Pathology, School of Dentistry, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan, 626-870, South Korea.
authors.forename: Vok Hee
authors.initials: VH
authors.lastname: Woo
authors.affiliation: Department of Periodontology, School of Dentistry, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan 626-870, South Korea.
authors.forename: Jeom Il
authors.initials: JI
authors.lastname: Choi
authors.affiliation: Department of Periodontology, School of Dentistry, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan 626-870, South Korea.
authors.forename: Seung Jo
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Oral Pathology, School of Dentistry, Kyungpook National University, Joong-gu, Daegu 700-412, South Korea.
authors.forename: Hong In
authors.initials: HI
authors.lastname: Shin
authors.affiliation: Department of Oral Pathology, School of Dentistry, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan, 626-870, South Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Oral Pathology, School of Dentistry, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan, 626-870, South Korea; Institute of Translational Dental Sciences, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan 626-870, South Korea. Electronic address: parkhr@pusan.ac.kr.
authors.forename: Hae Ryoun
authors.initials: HR
authors.lastname: Park
mesh_terms: D001343:Autophagy; D015153:Blotting, Western; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013194:Staining and Labeling
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D017382:Reactive Oxygen Species; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
keywords: Autophagy; G1 cell cycle arrest; Oral cancer; Porphyromonas gingivalis; Tumour microenvironment