scholarly journals Stromal Hedgehog pathway activation by IHH suppresses lung adenocarcinoma growth and metastasis by limiting reactive oxygen species

2019 ◽  
Author(s):  
Sahba Kasiri ◽  
Baozhi Chen ◽  
Alexandra N. Wilson ◽  
Annika Reczek ◽  
Simbarashe Mazambani ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Lung Tumor ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Pathway Activation ◽  
Hh Signaling

AbstractActivation of the Hedgehog (Hh) signaling pathway by mutations within its components drives the growth of several cancers. However, the role of Hh pathway activation in lung cancers has been controversial. We demonstrate that the Hh signaling pathway is activated in lung stroma in a paracrine manner. Genetic deletion of Shh in autochthonous murine lung adenocarcinoma had no effect on survival. Early abrogation of the pathway by an anti-SHH/IHH antibody 5E1 led to significantly worse survival with increased tumor and metastatic burden. Loss of IHH by in vivo CRISPR led to more aggressive tumor growth suggesting that IHH, not SHH, activates the pathway in stroma to drive its tumor suppressive effects - a novel role for IHH in the lung. Tumors from mice treated with 5E1 had decreased blood vessel density and increased reactive oxygen species (ROS). Treatment of KP mice with 5E1 and N-acetylcysteine, as a ROS scavenger, decreased tumor ROS levels, inhibited tumor growth and prolonged mouse survival suggesting that increased ROS levels from stromal Hh pathway inhibition spurred lung tumor growth. Thus, IHH induces stromal Hh pathway activation to suppress tumor growth and metastases, in part, by limiting ROS production.

scholarly journals Rare-Earth-Doped Calcium Carbonate Exposed to X-ray Irradiation to Induce Reactive Oxygen Species for Tumor Treatment

2019 ◽  
Vol 20 (5) ◽  
pp. 1148 ◽  
Author(s):  
Chun-Chen Yang ◽  
Wei-Yun Wang ◽  
Feng-Huei Lin ◽  
Chun-Han Hou
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Tumor Growth ◽  
Light Source ◽  
Reactive Oxygen ◽  
Blood Analysis ◽  
Oxygen Species ◽  
Tumor Treatment ◽  
X Ray

Conventional photodynamic therapy (PDT) is limited by its penetration depth due to the photosensitizer and light source. In this study, we developed X-ray induced photodynamic therapy that applied X-ray as the light source to activate Ce-doped CaCO3 (CaCO3:Ce) to generate an intracellular reactive oxygen species (ROS) for killing cancer cells. The A549 cell line was used as the in vitro and in vivo model to evaluate the efficacy of X-ray-induced CaCO3:Ce. The cell viability significantly decreased and cell cytotoxicity obviously increased with CaCO3:Ce exposure under X-ray irradiation, which is less harmful than radiotherapy in tumor treatment. CaCO3:Ce produced significant ROS under X-ray irradiation and promoted A549 cancer cell death. CaCO3:Ce can enhance the efficacy of X-ray induced PDT, and tumor growth was inhibited in vivo. The blood analysis and hematoxylin and eosin stain (H&E) stain fully supported the safety of the treatment. The mechanisms underlying ROS and CO2 generation by CaCO3:Ce activated by X-ray irradiation to induce cell toxicity, thereby inhibiting tumor growth, is discussed. These findings and advances are of great importance in providing a novel therapeutic approach as an alternative tumor treatment.

scholarly journals A water soluble parthenolide analog suppresses in vivo tumor growth of two tobacco-associated cancers, lung and bladder cancer, by targeting NF-κB and generating reactive oxygen species

2010 ◽  
Vol 128 (10) ◽  
pp. 2481-2494 ◽  
Author(s):  
Rajasubramaniam Shanmugam ◽  
Praveen Kusumanchi ◽  
Hitesh Appaiah ◽  
Liang Cheng ◽  
Peter Crooks ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Bladder Cancer ◽  
Tumor Growth ◽  
Reactive Oxygen ◽  
Water Soluble ◽  
Oxygen Species

scholarly journals 6′-O-Galloylpaeoniflorin Attenuates Osteoclasto-genesis and Relieves Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species and MAPKs/c-Fos/NFATc1 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjie Liu ◽  
Gang Xie ◽  
Guixin Yuan ◽  
Dantao Xie ◽  
Zhen Lian ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Bone Diseases ◽  
Cell Counting ◽  
Specific Gene ◽  
Oxygen Species ◽  
Ovariectomized Mice

Emerging evidence suggests bright prospects of some natural antioxidants in the treatment of osteoporosis. 6′-O-Galloylpaeoniflorin (GPF), an antioxidant isolated from peony roots (one of very widely used Oriental medicines, with various anti-inflammatory, antitumor, and antioxidant activities), shows a series of potential clinical applications. However, its effects on osteoporosis remain poorly investigated. The current study aimed to explore whether GPF can attenuate osteoclastogenesis and relieve ovariectomy-induced osteoporosis via attenuating reactive oxygen species (ROS), and investigate the possible mechanism. After the culture of primary murine bone marrow-derived macrophages/monocytes were induced by the use of macrophage colony-stimulating factor (M-CSF) and the receptor activator of NF-κB ligand (RANKL) and then treated with GPF. Cell proliferation and viability were assessed by Cell Counting Kit-8 (CCK-8) assay. Thereafter, the role of GPF in the production of osteoclasts and the osteogenic resorption of mature osteoclasts were evaluated by tartrate-resistant acid phosphatase (TRAP) staining, podosome belt formation, and resorption pit assay. Western blotting and qRT-PCR examination were performed to evaluate proteins’ generation and osteoclast-specific gene levels, respectively. The ROS generation in cells was measured in vitro by 2′,7′-Dichlorodi-hydrofluorescein diacetate (DCFH-DA). Ovariectomy-induced osteoporosis mouse administered with GPF or vehicle was performed to explore the in vivo potential of GPF, then a micro-CT scan was performed in combination with histological examination for further analysis. GPF suppressed the formation of osteoclasts and podosome belts, as well as bone resorption when induced by RANKL through affecting intracellular ROS activity, MAPKs signaling pathway, and subsequent NFATc1 translocation and expression, as well as osteoclast-specific gene expression in vitro. In vivo study suggested that exposure to GPF prevented osteoporosis-related bone loss in the ovariectomized mice. These findings indicate that GPF attenuates osteoclastogenesis and relieves ovariectomy-induced osteoporosis by inhibiting ROS and MAPKs/c-Fos/NFATc1 signaling pathway. This suggested that GPF may be potentially used to treat bone diseases like periodontitis, rheumatoid arthritis, and osteoporosis associated with osteoclasts.

scholarly journals Aspirin-Mediated Attenuation of Intervertebral Disc Degeneration by Ameliorating Reactive Oxygen Species In Vivo and In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-20 ◽  
Author(s):  
Yu Liu ◽  
Jiayi Lin ◽  
Xiexing Wu ◽  
Xiaobin Guo ◽  
Houyi Sun ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Ampk Signaling

Intervertebral disc (IVD) degeneration (IDD) is a major cause of low back pain. The pathogenesis of IDD is associated with the disturbance of reactive oxygen species (ROS) equilibrium, inflammation, and matrix loss. Aspirin is a nonsteroidal anti-inflammatory drug that effectively inhibits inflammation and oxidative stress and has been widely used for the treatment of back pain. Therefore, we hypothesize that aspirin reverses the IDD process via antioxidative and anti-inflammatory effects on the AMPK signaling pathway. In vitro, aspirin diminished cellular oxygen free radicals (ROS, nitric oxide (NO)) and inflammatory cytokines (interleukin- (IL-) 1β and IL-6 and tumor necrosis factor alpha (TNF-α)) induced by lipopolysaccharides (LPS) in nucleus pulposus cells (NPCs). We found that aspirin preserved the extracellular matrix (ECM) content of collagen type II (COL2) and aggrecan while inhibiting the expression of matrix-degenerating enzymes, including matrix metalloproteinase 3 and 13 (MMP-3 and MMP-13) and A disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS-4, ADAMTS-5). Aspirin significantly promoted the ratios of p-AMPK to AMPK and p-ACC to ACC expression in NPCs. Furthermore, pretreatment with the AMPK inhibitor compound C abrogated the antioxidant effects of aspirin. In vivo, an IDD model was established in Sprague-Dawley rats via percutaneous disc puncture with the 20-gauge needle on levels 8-9 and 9-10 of the coccygeal vertebrae. Imaging assessment showed that after aspirin treatment, improvements in disc height index (DHI) ranged from 1.22-fold to 1.54-fold and nucleus pulposus signal strength improved from 1.26-fold to 1.33-fold. Histological analysis showed that aspirin treatment prevented the loss of COL2 and decreased MMP-3 and MMP-13, inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, and TNF-α expression in the IVD tissues. These results suggest that treatment with aspirin could reverse the IDD process via the AMPK signaling pathway, which provides new insights into the potential clinical applications of aspirin, particularly for IDD treatment.

Influence of low-dose-rate red and near-infrared radiations on the level of reactive oxygen species, the genetic apparatus and the tumor growth in mice in vivo

BIOPHYSICS ◽  
2013 ◽  
Vol 58 (5) ◽  
pp. 712-717 ◽  
Author(s):  
S. I. Zaichkina ◽  
O. M. Rozanova ◽  
A. R. Dyukina ◽  
N. B. Simonova ◽  
S. P. Romanchenko ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Tumor Growth ◽  
Dose Rate ◽  
Low Dose ◽  
Near Infrared ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Genetic Apparatus ◽  
Low Dose Rate

scholarly journals Stromal Hedgehog pathway activation by IHH suppresses lung adenocarcinoma growth and metastasis by limiting reactive oxygen species

Oncogene ◽  
2020 ◽  
Vol 39 (16) ◽  
pp. 3258-3275
Author(s):  
Sahba Kasiri ◽  
Baozhi Chen ◽  
Alexandra N. Wilson ◽  
Annika Reczek ◽  
Simbarashe Mazambani ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lung Adenocarcinoma ◽  
Reactive Oxygen ◽  
Hedgehog Pathway ◽  
Oxygen Species ◽  
Pathway Activation

scholarly journals Increased formation of reactive oxygen species during tumor growth: Ex vivo low-temperature EPR and in vivo bioluminescence analyses

2020 ◽  
Vol 147 ◽  
pp. 167-174 ◽  
Author(s):  
Gang Cheng ◽  
Jing Pan ◽  
Radoslaw Podsiadly ◽  
Jacek Zielonka ◽  
Alexander M. Garces ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Low Temperature ◽  
Tumor Growth ◽  
Ex Vivo ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Targeting autophagy enhances atezolizumab-induced mitochondria-related apoptosis in osteosarcoma

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Zhuochao Liu ◽  
Hongyi Wang ◽  
Chuanzhen Hu ◽  
Chuanlong Wu ◽  
Jun Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Antitumor Immunity ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Specific Monoclonal Antibody ◽  
Osteosarcoma Cells ◽  
Jnk Pathway ◽  
In Vivo Experiments

AbstractIn this study, we identified the multifaceted effects of atezolizumab, a specific monoclonal antibody against PD-L1, in tumor suppression except for restoring antitumor immunity, and investigated the promising ways to improve its efficacy. Atezolizumab could inhibit the proliferation and induce immune-independent apoptosis of osteosarcoma cells. With further exploration, we found that atezolizumab could impair mitochondria of osteosarcoma cells, resulting in increased release of reactive oxygen species and cytochrome-c, eventually leading to mitochondrial-related apoptosis via activating JNK pathway. Nevertheless, the excessive release of reactive oxygen species also activated the protective autophagy of osteosarcoma cells. Therefore, when we combined atezolizumab with autophagy inhibitors, the cytotoxic effect of atezolizumab on osteosarcoma cells was significantly enhanced in vitro. Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.

Sign in / Sign up

Export Citation Format

Share Document