Low-level light therapy potentiates NPe6-mediated photodynamic therapy in a human osteosarcoma cell line via increased ATP

Shang-Ru Tsai; Rui Yin; Ying-Ying Huang; Bor-Ching Sheu; Si-Chen Lee; Michael R Hamblin

doi:10.1016/j.pdpdt.2014.10.009

Low-level light therapy potentiates NPe6-mediated photodynamic therapy in a human osteosarcoma cell line via increased ATP

Photodiagnosis Photodyn Ther. 2015 Mar;12(1):123-30. doi: 10.1016/j.pdpdt.2014.10.009. Epub 2014 Nov 13.

Authors

Shang-Ru Tsai¹, Rui Yin², Ying-Ying Huang³, Bor-Ching Sheu⁴, Si-Chen Lee⁵, Michael R Hamblin⁶

Affiliations

¹ 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.
² 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.
³ Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA; Department of Dermatology, Harvard Medical School, Boston, MA, USA.
⁴ College of Medicine, National Taiwan University, Taipei, Taiwan.
⁵ Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan; Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan.
⁶ 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.

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.

Keywords: Adenosine triphosphate; Low level light therapy; Lysosomal uptake; Mono-l-aspartyl chlorin(e6); Photobiomodulation; Photodynamic therapy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism*
Apoptosis / drug effects
Apoptosis / radiation effects
Cell Line, Tumor
Cell Survival / drug effects
Cell Survival / radiation effects
Combined Modality Therapy / methods
Humans
Low-Level Light Therapy / methods*
Osteosarcoma / metabolism*
Osteosarcoma / pathology
Osteosarcoma / therapy*
Photochemotherapy / methods*
Photosensitizing Agents / therapeutic use
Porphyrins / metabolism*
Treatment Outcome

Substances

Photosensitizing Agents
Porphyrins
Adenosine Triphosphate
Talaporfin

Abstract

Publication types

MeSH terms

Substances

Grants and funding