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Lasers in Medical Science        (2025) 40:38

https://doi.org/10.1007/s10103-025-04287-0[pic 1]

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Effects of photobiomodulation in mitochondrial quantity, biogenesis and mitophagy-associated genes in breast cancer cells

Larissa Alexsandra da Silva Neto Trajano1,2[pic 3] · Priscyanne Barreto Siqueira1[pic 4] · Daphne Pinheiro1[pic 5] · Thayssa Gomes Farias1[pic 6] · Márcia Soares dos Santos1 · Bruno Ricardo Barreto Pires1 ·

Adenilson de Souza da Fonseca1,3[pic 7] · Andre Luiz Mencalha1[pic 8]

Received: 12 April 2024 / Accepted: 5 January 2025

© The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2025

Abstract

In this article, we aim to evaluate the effects of photobiomodulation on mitochondria quantity, biogenesis, and mitophagy- associated genes in breast cancer (BC) cells. Both models were irradiated with a low-power infrared laser (880 nm, 150 mW) and amber LED (617 nm, 1500 mW), alone or simultaneously. We evaluated the mRNA expression of PINK1 and PGC-1α genes, and the mitochondrial number was assessed based on the ratio of mitochondrial DNA/genomic DNA (mtDNA/gDNA). No significant difference was observed in the mtDNA/gDNA ratio comparing the low-power infrared laser (LPIL) and LED-irradiated groups to their control counterparts. Similarly, no difference was observed in the mRNA levels of PINK1 and PGC-1α of the irradiated group with an LPIL and LED alone or in combination. In conclusion, PBM with LPIL and LED did not alter the mtDNA/gDNA ratio nor modulate the mRNA levels of the genes related to mitophagy and biogenesis in BC cells.

Keywords Photobiomodulation · Low-power infrared laser · LED · Mitophagy · mtDNA · Mitochondrial biogenesis

[pic 9]Introduction

Photobiomodulation (PBM) is defined as the use of red or near-infrared (NIR) light to heal, restore, and stimulate vari- ous physiological processes and to repair damage caused by injuries or diseases [1]. Photobiomodulation therapy (PBMT) utilizes low-power laser or light-emitting diodes (LEDs) at low fluences and irradiances. Its effects include stimulation  of  mitochondrial  metabolism,  increasing

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🖂 Larissa Alexsandra da Silva Neto Trajano larissa.alexsandra@hotmail.com

1        Departamento de Biofísica e Biometria Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Avenida 28 de Setembro, 87, fundos,

Vila Isabel, Rio de Janeiro 20551030, Brazil

2        Pró-Reitoria de Pesquisa e pós-graduação, Mestrado Profissional em Ciências Aplicadas em Saúde, Universidade de Vassouras, Avenida Expedicionário Oswaldo de Almeida Ramos, 280, Vassouras, Rio de Janeiro 27700000, Brazil

3        Departamento de Ciências Fisiológicas, Instituto Biomédico, niversidade Federal do Estado do Rio de Janeiro, Rua Frei Caneca, 94, 20211040 Rio de Janeiro, Brazil


adenosine triphosphate (ATP) production, cell prolifera- tion, differentiation, apoptosis, and migration, which result in therapeutic effects, such as pain control, healing injured tissues, and muscle repair [24].

Although the biological mechanisms of PBM’s therapeu- tic properties have not been fully elucidated, some authors have already suggested that PBM improves wound healing, reduces inflammation, prevents fibrosis, reduces pain, and enhances function in various tissues [5, 6]. Additionally, it has been reported that PBM has benefits in cancer patients, being effective in reducing side effects that result from can- cer therapy [1], such as oral mucositis [7] and lymphedema in breast cancer patients [8]. A study showed that combining Low-Level Laser Therapy (LLLT) with Complete Decon- gestive Therapy significantly reduced lymphedema symp- toms and improved limb mobility. The treatment followed a 4-week cycle using a standardized grid with color-coded holes. The application time of the LLLT was 1 min at each of the 10 points in the axilla, totaling 8 to 16 sessions [9]. However, the effects of PBMT in cancer patients have been questioned. Studies suggest that PBMT could influence cel- lular metabolic processes and stimulate the proliferation of malignant cells, potentially increasing tumor volume [10,

11]. Conversely, further studies are still required to demon- strate the relationship between PBM and tumor progression and to address whether PBM may negatively impact tumors [12, 13].

Mitochondria are critical organelles for tumor develop- ment and progression, providing the energy and macro- molecules necessary to modulate signaling processes that confer plasticity in changing environments [14]. Further- more, mitochondrial alterations affect tumorigenesis, mito- chondrial biogenesis and renewal, and cell death regulation [15]. Additionally, damaged mitochondria can be delivered to lysosomes for degradation through mitophagy. However, dysregulation of mitophagy impairs mitochondrial health in tumorigenesis and metastasis, potentially leading to autoph- agic cell death. Defective or impaired mitophagy leads to pathological conditions [15].

An accumulation of mutations in mitochondrial DNA (mtDNA) or a decrease in the number of mtDNA copies can affect energy production, resulting in the production of reactive oxygen species (ROS) and cell survival [16]. Alterations in copy number, point mutations, insertions, and large-scale deletions of the mtDNA, have been observed in several tumors, including breast cancer (BC) [17]. BC is a heterogeneous disease with various pathological out- comes [18]. Some studies have reported that mitochondrial dysfunctions are associated with the development of BC [19, 20]. Here, we aimed to evaluate the effects of photo- biomodulation in mitochondrial quantity, biogenesis, and

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