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 1.5 J/cm2 of 810 nm near infrared radiation (NIR) followed by addition of 10 μM NPe6 and after 2 h incubation by 1.5 J/cm2 of 652 nm 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.

Skin reactions after photodynamic therapy are unaffected by 839 nm photobiomodulation therapy: A randomized, double‐blind, placebo‐controlled, clinical trial

“…B). However, in vitro studies showed that PBM can increase ATP production and increase the expression of mitochondrial benzodiazepine receptors, thereby promoting mitochondrial PpIX synthesis that may enhance the phototoxicity of PDT . We did not investigate if PBM altered the cellular PpIX distribution, but PBM did not appear to increase PpIX synthesis as the median total amount of skin surface PpIX fluorescence was similar between skin exposed to PBM and placebo‐PBM.…”

Retrospective evaluation of the safety of low-level laser therapy/photobiomodulation in patients with head/neck cancer

“…2 Time to local recurrence some recent ex vivo experiments suggest a possible adverse effect of PBM on head/neck cancer cell [21]. Actually, some recent laboratory observations suggest that PBM might sensitize cancer cells to radiation [22] or increase apoptosis [23], both being potentially promising strategies that could be applied in the clinic.…”

Low level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 1: mechanisms of action, dosimetric, and safety considerations

“…On the contrary, Schartinger et al [91] observed a pro-apoptotic effect of PBM in head and neck SCC cells, whereas no anti-apoptotic effects occurred that might promote tumor cell resistance to cancer therapy. Increased apoptosis of human osteosarcoma cells was also induced by the administration of NIR (810 nm, continuous wave, 20 mW/cm 2 , 1.5 J/cm 2 ) prior to NPe6-mediated photodynamic therapy as a result of increased cellular ATP and a higher uptake of the photosensitizer [92]. Recently, it was reported that PBM administered to normal human lymphoblasts and leukemia cells prior to RT, resulted in a differential response of normal versus malignant cells suggesting that PBM does not confer protection and may even sensitize cancer cells to RT-induced killing [93].…”