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

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.

2019 ◽  
Vol 20 (9) ◽  
pp. 2072 ◽  
Author(s):  
Chun-Chen Yang ◽  
Min-Hsiung Tsai ◽  
Keng-Yuan Li ◽  
Chun-Han Hou ◽  
Feng-Huei Lin

Traditional photodynamic therapy (PDT) is limited by the penetration depth of visible light. Although the light source has been changed to near infrared, infrared light is unable to overcome the penetration barrier and it is only effective at the surface of the tumors. In this study, we used X-ray as a light source for deep-seated tumor treatment. A particle with a narrow band gap when exposed to soft X-rays would produce reactive oxygen species (ROS) to kill tumor cell, with less damage to the normal tissues. Anatase TiO2 has been studied as a photosensitizer in PDT. In the experiment, C was doped into the anatase lattice at an optimum atomic ratio to make the band gap narrower, which would be activated by X-ray to produce more ROS and kill tumor cells under stress. The results showed that the synthesized TiO2:C particles were identified as crystal structures of anatase. The synthesized particles could be activated effectively by soft X-rays to produce ROS, to degrade methylene blue by up to 30.4%. Once TiO2:C was activated by X-ray irradiation, the death rate of A549 cells in in vitro testing was as high as 16.57%, on day 2. In the animal study, the tumor size gradually decreased after treatment with TiO2:C and exposure to X-rays on day 0 and day 8. On day 14, the tumor declined to nearly half of its initial volume, while the tumor in the control group was twice its initial volume. After the animal was sacrificed, blood, and major organs were harvested for further analysis and examination, with data fully supporting the safety of the treatment. Based on the results of the study, we believe that TiO2:C when exposed to X-rays could overcome the limitation of penetration depth and could improve PDT effects by inhibiting tumor growth effectively and safely, in vivo.


2010 ◽  
Vol 128 (10) ◽  
pp. 2481-2494 ◽  
Author(s):  
Rajasubramaniam Shanmugam ◽  
Praveen Kusumanchi ◽  
Hitesh Appaiah ◽  
Liang Cheng ◽  
Peter Crooks ◽  
...  

2017 ◽  
Vol 16 (11) ◽  
pp. 1623-1630 ◽  
Author(s):  
Wei Zhu ◽  
Ying-Hua Gao ◽  
Chun-Hong Song ◽  
Zhi-Bin Lu ◽  
Tabbisa Namulinda ◽  
...  

Upon light activation, 13a can induce the production of PpIX in vivo which produces ROS and other reactive oxygen species to lead to the apoptosis of S180 cell tumors.


2019 ◽  
Author(s):  
Sahba Kasiri ◽  
Baozhi Chen ◽  
Alexandra N. Wilson ◽  
Annika Reczek ◽  
Simbarashe Mazambani ◽  
...  

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.


2019 ◽  
Author(s):  
Liyi Huang ◽  
Haidan Lin ◽  
Qing Chen ◽  
Lehua Yu ◽  
dingqun bai

Abstract Abstract Background: Breast cancer is one of the most commonly diagnosed cancers in women, with high morbidity and mortality. Tumor metastasis is implicated in most breast cancer deaths; thus, inhibiting metastasis may provide a therapeutic direction for breast cancer. In the present study, pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) was used to inhibit metastasis in MCF-7 breast cancer cells. Methods: Uptake of MPPa was detected by fluorescence microscopy. Cell viability was evaluated by the Cell Counting Kit-8 (CCK-8). ROS generation was detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The migration of cells was assessed by wound healing assay, and invasion ability was assessed by Matrigel invasion assay. Levels of MMP2 and MMP9 were measured by PCR. Akt, phospho-Akt (Ser473), phospho-NF-κB p65 (Ser536) and NF-κB p65 were measured by western blotting. The F-actin cytoskeleton was observed by immunofluorescence. Lung tissue was visualized by hematoxylin and eosin staining. Results: Following MPPa-PDT, migration and invasion were decreased in the MCF-7 cells. MPPa-PDT downregulated the expression of MMP2 and MMP9, which are responsible for the initiation of metastasis. MPPa-PDT reduced the phosphorylation of Akt and NF-κB. MPPa-PDT also reduced and destroyed the F-actin cytoskeleton in MCF-7 cells. These effects were blocked by the reactive oxygen species scavenger NAC or the Akt activator SC79, while the PI3K inhibitor LY294002 or the Akt inhibitor triciribine enhanced these effects. Moreover, MPPa-PDT inhibited tumor metastasis and destroyed F-actin in vivo. Conclusion: Taken together, these results demonstrate that MPPa-PDT inhibits the metastasis of MCF-7 cells both in vitro and in vivo and may be involved in the Akt/NF-κB-dependent MMP-9 signaling pathway. Thus, MPPa-PDT may be a promising treatment to inhibit metastasis. Key words: photodynamic therapy, reactive oxygen species, breast tumor, migration, invasion


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 ◽  
...  

2020 ◽  
Vol 8 (26) ◽  
pp. 5707-5721
Author(s):  
Mingdi Sun ◽  
Dan Yang ◽  
Wu Fanqi ◽  
Zhao Wang ◽  
Hongjiao Ji ◽  
...  

Photodynamic therapy (PDT) is a light-based modality for tumor treatment that involves the generation of reactive oxygen species (ROS) by the combination of light, a photosensitizer, and molecular oxygen.


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