Blue LED causes autophagic cell death in human osteosarcoma by increasing ROS generation and dephosphorylating EGFR

He, Mingyu; Yan, Gege; Wang, Yang; Gong, Rui; Hong, Lei; Yu, Shuting; He, Xiaoqi; Li, Guanghui; Du, Weijie; Ma, Tianshuai; Gao, Ming; Yu, Meixi; Liu, Shenzhen; Xu, Zihang; Idiiatullina, Elina; Zagidullin, Naufal; Павлов, В. Н.; Cai, Benzhi; Yuan, Ye; Yang, Lei

doi:10.1111/jcmm.16412

Cited by 9 publications

(15 citation statements)

References 52 publications

(84 reference statements)

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“…When MYC was knocked down or MBTPS2 was overexpressed, the expression of Beclin-1 and LC3 was suppressed, while the P62 expression increased. These findings suggested that autophagy in osteosarcoma cells was inhibited, which was consistent with previous studies [ 34 – 36 ]. Conclusively, we confirmed the correlation of MYC or MBTPS2 with autophagy and metastasis in osteosarcoma, which provides further verification of the validity of the model.…”

Section: Discussionsupporting

confidence: 93%

Construction and validation of a prognostic model for osteosarcoma patients based on autophagy-related genes

Ning

Liu

et al. 2022

Discov Onc

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Background Osteosarcoma is the most frequent primary bone malignancy with a poor prognosis because of pulmonary metastasis. Autophagy is strongly associated with tumor metastasis, and it is valuable to construct an autophagy-related gene risk model for predicting the prognosis of osteosarcoma. Methods We obtained ARGs from the Human Autophagy Database and RNA-sequencing data of osteosarcoma patients from the Gene Expression Omnibus (GEO) database. Subsequently, univariate and multivariate cox regression analyses were performed to construct a three-gene prognostic model and its accuracy was further confirmed in the Therapeutic Applications Research to Generate Effective Treatments (TARGET) database. Afterward, we detected the expression levels and effects on osteosarcoma cells metastasis of MYC and MBTPS2, which were involved in the model. Results In both training and verification cohorts, patients with lower risk scores had longer OS, and the model was identified as an independent prognostic factor in osteosarcoma. Besides, the ROC curve demonstrated the reliability of the model. Furthermore, RT-qPCR, Western Blotting and IHC results indicated that MYC and MBTPS2 were differently expressed in osteosarcoma tissues and cell lines. MYC knockdown or MBTPS2 overexpression prevented the capacity of migration and invasion in osteosarcoma cell lines through inhibiting cellular autophagy. Conclusion The risk model based on three ARGs had a strong ability to predict the prognosis of osteosarcoma patients. Our findings also suggested that MYC and MBTPS2 were two major factors regulating autophagy in osteosarcoma, and could serve as potential therapeutic targets for osteosarcoma.

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Section: Discussionsupporting

confidence: 93%

Construction and validation of a prognostic model for osteosarcoma patients based on autophagy-related genes

Ning

Liu

et al. 2022

Discov Onc

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“…Besides, He et al. (2021) found that blue LED PBMT effectively causes autophagic cell death in human OS cells, which was induced by promoting ROS and the EGFR/Beclin-1-mediated signaling pathway ( 98 ). Recently, Shoorche et al.…”

Section: Phototherapy Of Osteosarcomamentioning

confidence: 99%

“…Blue light, as a visible light with a wavelength range of 400–500 nm, has been clinically applied successfully comprising neonatal jaundice, psoriasis (Pv), atopic dermatitis (AD), eczema, acne, and other inflammatory skin conditions, although the number of available clinical studies evaluating the efficacy of blue light treatment is still limited ( 103 , 136 ). Furthermore, recent studies have demonstrated that blue light irradiation inhibits the proliferation of multiple types of cancer cells in vitro and in vivo , including colon cancer cells ( 14 , 144 , 145 ), malignant glioma cells ( 12 ), melanoma cells ( 10 , 146 , 147 ), B-cell lymphoma cells ( 13 ), fibrosarcoma cells ( 14 ), pancreatic cancer cells ( 15 ), cutaneous squamous cell carcinoma cells (CSCC), epidermoid carcinoma cells ( 148 , 149 ), leukemia cells (Kasumi-1) ( 150 ), bladder cancer cells ( 151 ), colorectal cancer cells ( 152 , 153 ), breast cancer cells ( 91 ), and human OS cells ( 95 , 98 ). Here, we have briefly summarized the relevant research of blue light PBMT in the field of cancer treatment ( Table 1 ).…”

Section: Blue Light Photobiomodulation Therapy In Cancer Treatmentmentioning

confidence: 99%

“…Additionally, He et al. (2021) evaluated the antitumor effects of LED blue light therapy individually on human OS cells for the first time, and the results showed that blue LED irradiation significantly inhibited the proliferation, migration, and invasion of human OS cells by triggering ROS, inducing cell apoptosis and autophagy pathways, providing a potential approach and strategy for human OS treatment ( 98 ). Also, the investigators found that circadian rhythm may be closely related to endogenous control of tumor progression, including pancreatic adenocarcinoma ( 155 ), Glasgow osteosarcoma ( 155 ), breast cancer ( 156 ), and colorectal tumor ( 157 ).…”

Section: Blue Light Photobiomodulation Therapy In Cancer Treatmentmentioning

confidence: 99%

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Progress of phototherapy for osteosarcoma and application prospect of blue light photobiomodulation therapy

Yang

Jiang

et al. 2022

Front. Oncol.

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Osteosarcoma (OS) is the most common primary malignant bone tumor that mainly affects the pediatric and adolescent population; limb salvage treatment has become one of the most concerned and expected outcomes of OS patients recently. Phototherapy (PT), as a novel, non-invasive, and efficient antitumor therapeutic approach including photodynamic therapy (PDT), photothermal therapy (PTT), and photobiomodulation therapy (PBMT), has been widely applied in superficial skin tumor research and clinical treatment. OS is the typical deep tumor, and its phototherapy research faces great limitations and challenges. Surprisingly, pulse mode LED light can effectively improve tissue penetration and reduce skin damage caused by high light intensity and has great application potential in deep tumor research. In this review, we discussed the research progress and related molecular mechanisms of phototherapy in the treatment of OS, mainly summarized the status quo of blue light PBMT in the scientific research and clinical applications of tumor treatment, and outlooked the application prospect of pulsed blue LED light in the treatment of OS, so as to further improve clinical survival rate and prognosis of OS treatment and explore corresponding cellular mechanisms.

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“… 7 , 8 Furthermore, light irradiation at wavelengths ranging from 450 to 495 nm, which human eyes perceive as blue, has been shown to have antitumor effects on various cancer cells, including melanoma, 9 , 10 lymphoma, 11 colon cancer, 12 , 13 , 14 , 15 leukemia, 16 pancreatic cancer, 17 and osteosarcoma. 18 Therefore, blue light (BL) from LEDs is expected to become a novel non‐invasive therapeutic option in cancer treatment. Although the biological mechanism of BL‐induced antitumor effect is reported to be regulated by cell cycle inhibition, 9 reactive oxygen species, 18 , 19 , 20 , 21 apoptosis, 9 , 12 , 17 , 20 , 22 and autophagy, 11 , 12 , 14 , 18 its role and precise mechanisms remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Blue light induces apoptosis and autophagy by promoting ROS‐mediated mitochondrial dysfunction in synovial sarcoma

et al. 2023

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Background Synovial sarcoma (SS) has limited treatment options and there is an urgent need to develop a novel therapeutic strategy to treat SS. Blue light (BL) has been shown to inhibit the growth of several cancer cells. However, the efficacy of BL in soft tissue sarcomas such as SS has not been demonstrated, and the detailed mechanism underlying the antitumor activity of BL is not fully understood. In this study, we investigated the antitumor effect of BL on SS. Methods Human SS cell lines were continuously irradiated with BL using light‐emitting diodes (LEDs) in an incubator for in vitro analysis. The chicken chorioallantoic membrane (CAM) tumors and xenograft tumors in mice were subjected to daily BL irradiation with LEDs. Results BL caused growth inhibition of SS cells and histological changes in CAM tumors. BL also suppressed the migration and invasion abilities of SS cells. The type of cell death in SS cells was revealed to be apoptosis. Furthermore, BL induced excessive production of reactive oxygen species (ROS) in mitochondria, resulting in oxidative stress and malfunctioned mitochondria. Reducing the production of ROS using N‐acetylcysteine (NAC), a ROS scavenger, attenuated the inhibitory effect of BL on SS cells and mitochondrial dysfunction. In addition, BL induced autophagy, which was suppressed by the administration of NAC. The autophagy inhibitor of 3‐methyladenine and small interfering RNA against the autophagy marker light chain 3B facilitated apoptotic cell death. Moreover, BL suppressed tumor growth in a mouse xenograft model. Conclusion Taken together, our results revealed that BL induced apoptosis via the ROS‐mitochondrial signaling pathway, and autophagy was activated in response to the production of ROS, which protected SS cells from apoptosis. Therefore, BL is a promising candidate for the development of an antitumor therapeutic strategy targeting SS.

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Blue LED causes autophagic cell death in human osteosarcoma by increasing ROS generation and dephosphorylating EGFR

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 9 publications

References 52 publications

Construction and validation of a prognostic model for osteosarcoma patients based on autophagy-related genes

Construction and validation of a prognostic model for osteosarcoma patients based on autophagy-related genes

Progress of phototherapy for osteosarcoma and application prospect of blue light photobiomodulation therapy

Blue light induces apoptosis and autophagy by promoting ROS‐mediated mitochondrial dysfunction in synovial sarcoma

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