title: Low-level light therapy potentiates NPe6-mediated photodynamic therapy in a human osteosarcoma cell line via increased ATP.
abstract: BACKGROUND
  Low-level light therapy (LLLT) is used to stimulate healing, reduce pain and inflammation, and preserve tissue from dying. LLLT has been shown to protect cells in culture from dying after various cytotoxic insults, and LLLT is known to increase the cellular ATP content. Previous studies have demonstrated that maintaining a sufficiently high ATP level is necessary for the efficient induction and execution of apoptosis steps after photodynamic therapy (PDT).
  
  
  METHODS
  We asked whether LLLT would protect cells from cytotoxicity due to PDT, or conversely whether LLLT would enhance the efficacy of PDT mediated by mono-l-aspartyl chlorin(e6) (NPe6). Increased ATP could lead to enhanced cell uptake of NPe6 by the energy dependent process of endocytosis, and also to more efficient apoptosis. In this study, human osteosarcoma cell line MG-63 was subjected to 1.5J/cm(2) of 810nm near infrared radiation (NIR) followed by addition of 10μM NPe6 and after 2h incubation by 1.5J/cm(2) of 652nm red light for PDT.
  
  
  RESULTS
  PDT combined with LLLT led to higher cell death and increased intracellular reactive oxygen species compared to PDT alone. The uptake of NPe6 was moderately increased by LLLT, and cellular ATP was increased. The mitochondrial respiratory chain inhibitor antimycin A abrogated the LLLT-induced increase in cytotoxicity.
  
  
  CONCLUSIONS
  Taken together, these results demonstrate that LLLT potentiates NPe6-mediated PDT via increased ATP synthesis and is a potentially promising strategy that could be applied in clinical PDT.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA; Department of Dermatology, Harvard Medical School, Boston, MA, USA; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
authors.forename: Shang-Ru
authors.initials: SR
authors.lastname: Tsai
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA; Department of Dermatology, Harvard Medical School, Boston, MA, USA; Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yin
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA; Department of Dermatology, Harvard Medical School, Boston, MA, USA.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Huang
authors.affiliation: College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Bor-Ching
authors.initials: BC
authors.lastname: Sheu
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan; Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Si-Chen
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA; Department of Dermatology, Harvard Medical School, Boston, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA. Electronic address: Hamblin@helix.mgh.harvard.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy / Q000379:methods; D006801:Humans; D028022:Low-Level Light Therapy / Q000379:methods*; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011166:Porphyrins / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D000255:Adenosine Triphosphate; C053434:Talaporfin
keywords: Adenosine triphosphate; Low level light therapy; Lysosomal uptake; Mono-l-aspartyl chlorin(e6); Photobiomodulation; Photodynamic therapy