RelA-Mediated BECN1 Expression Is Required for Reactive Oxygen Species-Induced Autophagy in Oral Cancer Cells Exposed to Low-Power Laser Irradiation

PLoS One. 2016 Sep 15;11(9):e0160586. doi: 10.1371/journal.pone.0160586. eCollection 2016.

Abstract

Low-power laser irradiation (LPLI) is a non-invasive and safe method for cancer treatment that alters a variety of physiological processes in the cells. Autophagy can play either a cytoprotective role or a detrimental role in cancer cells exposed to stress. The detailed mechanisms of autophagy and its role on cytotoxicity in oral cancer cells exposed to LPLI remain unclear. In this study, we showed that LPLI at 810 nm with energy density 60 J/cm2 increased the number of microtubule associated protein 1 light chain 3 (MAP1LC3) puncta and increased autophagic flux in oral cancer cells. Moreover, reactive oxygen species (ROS) production was induced, which increased RelA transcriptional activity and beclin 1 (BECN1) expression in oral cancer cells irradiated with LPLI. Furthermore, ROS scavenger or knockdown of RelA diminished LPLI-induced BECN1 expression and MAP1LC3-II conversion. In addition, pharmacological and genetic ablation of autophagy significantly enhanced the effects of LPLI-induced apoptosis in oral cancer cells. These results suggest that autophagy may be a resistant mechanism for LPLI-induced apoptosis in oral cancer cells.

MeSH terms

  • Autophagy*
  • Beclin-1 / metabolism*
  • Humans
  • Low-Level Light Therapy
  • Mouth Neoplasms / immunology
  • Mouth Neoplasms / pathology*
  • NF-kappa B / metabolism
  • Reactive Oxygen Species / metabolism*
  • Transcription Factor RelA / metabolism*

Substances

  • BECN1 protein, human
  • Beclin-1
  • NF-kappa B
  • RELA protein, human
  • Reactive Oxygen Species
  • Transcription Factor RelA

Grants and funding

This work was supported by National Science Council (NSC 101 and 102-2311-B-075B-001 to C.W. Shu), Kaohsiung Veterans General Hospital (VGHKS99-072 to Y.D. Hsieh and VGHKS102-007 to C.W. Shu), and Kaohsiung Veterans General Hospital, Pingtung Branch (P-001 to Y.D. Hsieh). Co-author Sam Wu is employed by Samwell Testing INC. Samwell Testing INC provided support in the form of salary for author SW, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the “author contributions” section.