Pro‐apoptotic Noxa is involved in ablative focal irradiation‐induced lung injury

Kim, Jee Youn; An, Yong Min; Choi, Won Hoon; Kim, Jin Mo; Cho, Samju; Yoo, Byung Rok; Kang, Ji-Won; Lee, Yun Sil; Lee, Yoon Jin; Cho, Jaeho

doi:10.1111/jcmm.13014

Cited by 8 publications

(8 citation statements)

References 30 publications

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“…On the other hand, the activation of MDA5 by Semliki Forest virus induces both caspase-9-mediated apoptosis and caspase-8-mediated extrinsic apoptosis (27). Since ionizing radiation can modulate the intrinsic and extrinsic apoptotic pathway (28)(29)(30)(31), further studies are needed to clarify the apoptotic pathway which RLR agonist and ionizing radiation cooperatively activate.…”

Section: Discussionmentioning

confidence: 99%

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer inï¿½vitro

et al. 2018

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Abstract. Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns and induce antiviral immune responses. Recent studies have demonstrated that RLR activation induces antitumor immunity and cytotoxicity against different types of cancer, including lung cancer. However a previous report has demonstrated that ionizing radiation exerts a limited effect on RLR in human monocytic cell-derived macrophages, suggesting that RLR agonists may be used as effective immunostimulants during radiation therapy. However, it is unclear whether ionizing radiation affects the cytotoxicity of RLR agonists against cancer cells. Therefore, in the present study the effects of cotreatment with ionizing radiation and RLR agonists on cytotoxicity against human non-small cell lung cancer cells A549 and H1299 was investigated. Treatment with RLR agonist poly(I:C)/LyoVec™ [poly(I:C)] exerted cytotoxic effects against human non-small cell lung cancer. The cytotoxic effects of poly(I:C) were enhanced by cotreatment with ionizing radiation, and poly(I:C) pretreatment resulted in the radiosensitization of non-small cell lung cancer. Furthermore, cotreatment of A549 and H1299 cells with poly(I:C) and ionizing radiation effectively induced apoptosis in a caspase-dependent manner compared with treatment with poly(I:C) or ionizing radiation alone. These results indicate that RLR agonists and ionizing radiation cotreatment effectively exert cytotoxic effects against human non-small cell lung cancer through caspase-mediated apoptosis.

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Section: Discussionmentioning

confidence: 99%

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer inï¿½vitro

et al. 2018

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“…Pmaip1 is a pro-apoptotic Bcl-2 homology domain 3-only protein [ 31 ]. It has been demonstrated that the Pmaip1-mediated pathway plays an important part in IR-induced apoptotic response [ 41 , 42 , 43 ]. Pmaip1 knockout mice showed resistance to IR-induced intestinal crypt cell apoptosis and survived longer than WT mice [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor Protects against Radiation-Induced Intestinal Injury in Mice via Inhibition of Intestinal Crypt Stem/Progenitor Cell Apoptosis

Lin

Luo

et al. 2021

Nutrients

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It is urgent to seek new potential targets for the prevention or relief of gastrointestinal syndrome in clinical radiation therapy for cancers. Vitamin D, mediated through the vitamin D receptor (VDR), has been identified as a protective nutrient against ionizing radiation (IR)-induced damage. This study investigated whether VDR could inhibit IR-induced intestinal injury and explored underlying mechanism. We first found that vitamin D induced VDR expression and inhibited IR-induced DNA damage and apoptosis in vitro. VDR was highly expressed in intestinal crypts and was critical for crypt stem/progenitor cell proliferation under physiological conditions. Next, VDR-deficient mice exposed to IR significantly increased DNA damage and crypt stem/progenitor cell apoptosis, leading to impaired intestinal regeneration as well as shorter survival time. Furthermore, VDR deficiency activated the Pmaip1-mediated apoptotic pathway of intestinal crypt stem/progenitor cells in IR-treated mice, whereas inhibition of Pmaip1 expression by siRNA transfection protected against IR-induced cell apoptosis. Therefore, VDR protects against IR-induced intestinal injury through inhibition of crypt stem/progenitor cell apoptosis via the Pmaip1-mediated pathway. Our results reveal the importance of VDR level in clinical radiation therapy, and targeting VDR may be a useful strategy for treatment of gastrointestinal syndrome.

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“…Thus, PM014 is an effective drug for reducing irradiated mediated fibroblast differentiation. In our previous study, we identified a new molecular mechanism underlying IR-induced fibrosis by demonstrating that Noxa-induced apoptosis plays an important role in fibrosis 22 . As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Cells were cultured on coverslips coated with poly- L -lysine, fixed with 4% paraformaldehyde in PBS and permeabilised with 0.1% Triton X-100 22 . The cells were incubated with primary antibodies at 4 °C overnight, and then stained with secondary antibodies.…”

Section: Methodsmentioning

confidence: 99%

“…S5). The pro-apoptotic protein Noxa is reportedly involved in radiation-induced lung fibrosis 22 . Immunohistochemistry and western blotting showed higher expression levels of Noxa in irradiated lungs than in control lungs, and that PM014 attenuated these IR-induced increases in Noxa expression ( Fig.…”

Section: Pm014 Attenuates Ir-induced Apoptosis In Alveolar Epithelialmentioning

confidence: 99%

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PM014 attenuates radiation-induced pulmonary fibrosis via regulating NF-kB and TGF-b1/NOX4 pathways

Park

Kim

et al. 2020

Sci Rep

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Radiation therapy is the mainstay in the treatment of lung cancer, and lung fibrosis is a radiotherapy-related major side effect that can seriously reduce patient’s quality of life. Nevertheless, effective strategies for protecting against radiation therapy-induced fibrosis have not been developed. Hence, we investigated the radioprotective effects and the underlying mechanism of the standardized herbal extract PM014 on radiation-induced lung fibrosis. Ablative radiation dose of 75 Gy was focally delivered to the left lung of mice. We evaluated the effects of PM014 on radiation-induced lung fibrosis in vivo and in an in vitro model. Lung volume and functional changes were evaluated using the micro-CT and flexiVent system. Fibrosis-related molecules were evaluated by immunohistochemistry, western blot, and real-time PCR. A orthotopic lung tumour mouse model was established using LLC1 cells. Irradiated mice treated with PM014 showed a significant improvement in collagen deposition, normal lung volume, and functional lung parameters, and these therapeutic effects were better than those of amifostine. PM104 attenuated radiation-induced increases in NF-κB activity and inhibited radiation-induced p65 translocation, ROS production, DNA damage, and epithelial-mesenchymal transition. PM104 effectively alleviated fibrosis in an irradiated orthotopic mouse lung tumour model while not attenuating the efficacy of the radiation therapy by reduction of the tumour. Standardized herbal extract PM014 may be a potential therapeutic agent that is able to increase the efficacy of radiotherapy by alleviating radiation-induced lung fibrosis.

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Pro‐apoptotic Noxa is involved in ablative focal irradiation‐induced lung injury

Cited by 8 publications

References 30 publications

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer inï¿½vitro

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer inï¿½vitro

Vitamin D Receptor Protects against Radiation-Induced Intestinal Injury in Mice via Inhibition of Intestinal Crypt Stem/Progenitor Cell Apoptosis

PM014 attenuates radiation-induced pulmonary fibrosis via regulating NF-kB and TGF-b1/NOX4 pathways

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