Abstract:Worldwide, cancer ranks as a leading cause of death and a crucial barrier to increasing life expectancy. An estimated 19.3 million new cases and almost 10 million deaths have occurred from cancer in 2020. 1 Despite numerous research efforts in understanding cancer and in developing anticancer strategies, cancer remains a major lethal disease in people.Reactive oxygen species (ROS) have been extensively studied in various human diseases, including cancers. ROS are normal byproducts of a wide variety of cellular… Show more
“…ROS play two roles during cell metabolism: at low to moderate levels, ROS act as a signal transducer to activate cell proliferation, migration, invasion and angiogenesis; however, high levels of ROS can cause damage to proteins, nucleic acids, lipids, cell membranes and organelles, resulting in cell death. 29 In this experiment, LIFU irradiation was used to exogenously manipulate ROS levels through SDT and ensure antitumor efficacy after LIFU irradiation was applied for 2 and 4 min. Figure 4 CLSM images of HeLa cells dyed with DCFH-DA after various treatments ( A ).…”
Background: Some patients with cervical cancer have the need to preserve fertility; therefore, a minimally invasive treatment option that can effectively inactivate tumors in these patients is necessary. Methods: In this paper, we designed and prepared nanoparticles (NPs) carrying IR780 and perfluorohexane (PFH) and characterized their properties. We focused on the promotion of programmed low-intensity focused ultrasound (LIFU) irradiation on the penetration and treatment of cervical cancer. First we used penetration-enhancing LIFU irradiation to promote the penetration of the NPs into 3D multicellular tumor spheroids (MCTSs) and tumors in tumor-bearing nude mice. Then we used re-therapeutic LIFU irradiation to achieve antitumor effects in vitro and in vivo. Photoacoustic (PA) and magnetic resonance (MR) imaging were used to monitor and evaluate the targeting and therapeutic effects of these NPs on tumor tissues.
Results:The NPs prepared in this paper exhibited high affinity for HeLa cells, and can selectively achieve mitochondrial localization in the cell due to IR780 assistance. The penetration-enhancing LIFU irradiation have the ability to promote the penetration of the NPs into cervical cancer models in vivo and in vitro. Under LIFU irradiation, the cytotoxic reactive oxygen species (ROS) produced by IR780 during the first half of the re-therapeutic LIFU irradiation and the physical acoustic droplet vaporization (ADV) effect after PFH phase transition during the second half of the re-therapeutic LIFU irradiation can achieve synergistic minimally invasive treatment of tumors, which can be visualized and evaluated by PA and MR imaging in vivo.
Conclusion:Well-programmed LIFU irradiation can promote NP penetration into deep tumor tissue and achieve antitumor effects simultaneously. Linking ROS + ADV effects can induce cell coagulation necrosis and lead to a comprehensive, long-term impact on tumor tissue, providing a conceptual theranostic nanoplatform for cervical cancer.
“…ROS play two roles during cell metabolism: at low to moderate levels, ROS act as a signal transducer to activate cell proliferation, migration, invasion and angiogenesis; however, high levels of ROS can cause damage to proteins, nucleic acids, lipids, cell membranes and organelles, resulting in cell death. 29 In this experiment, LIFU irradiation was used to exogenously manipulate ROS levels through SDT and ensure antitumor efficacy after LIFU irradiation was applied for 2 and 4 min. Figure 4 CLSM images of HeLa cells dyed with DCFH-DA after various treatments ( A ).…”
Background: Some patients with cervical cancer have the need to preserve fertility; therefore, a minimally invasive treatment option that can effectively inactivate tumors in these patients is necessary. Methods: In this paper, we designed and prepared nanoparticles (NPs) carrying IR780 and perfluorohexane (PFH) and characterized their properties. We focused on the promotion of programmed low-intensity focused ultrasound (LIFU) irradiation on the penetration and treatment of cervical cancer. First we used penetration-enhancing LIFU irradiation to promote the penetration of the NPs into 3D multicellular tumor spheroids (MCTSs) and tumors in tumor-bearing nude mice. Then we used re-therapeutic LIFU irradiation to achieve antitumor effects in vitro and in vivo. Photoacoustic (PA) and magnetic resonance (MR) imaging were used to monitor and evaluate the targeting and therapeutic effects of these NPs on tumor tissues.
Results:The NPs prepared in this paper exhibited high affinity for HeLa cells, and can selectively achieve mitochondrial localization in the cell due to IR780 assistance. The penetration-enhancing LIFU irradiation have the ability to promote the penetration of the NPs into cervical cancer models in vivo and in vitro. Under LIFU irradiation, the cytotoxic reactive oxygen species (ROS) produced by IR780 during the first half of the re-therapeutic LIFU irradiation and the physical acoustic droplet vaporization (ADV) effect after PFH phase transition during the second half of the re-therapeutic LIFU irradiation can achieve synergistic minimally invasive treatment of tumors, which can be visualized and evaluated by PA and MR imaging in vivo.
Conclusion:Well-programmed LIFU irradiation can promote NP penetration into deep tumor tissue and achieve antitumor effects simultaneously. Linking ROS + ADV effects can induce cell coagulation necrosis and lead to a comprehensive, long-term impact on tumor tissue, providing a conceptual theranostic nanoplatform for cervical cancer.
“…ROS, a normal byproduct of various cellular processes, can modulate gene expression in growth, development, and apoptosis ( 40 ). ROS has a double-edged sword effect on cell metabolism as a signal transducer.…”
Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-β1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-β1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-β type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-β1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-β1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-β1 into activated TGF-β1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.
“…Additionally, several matrix metalloproteinases (MMPs) participate in the proteolytic degradation of the ECM during the cancer invasion processes [ 2 , 9 ]. On the other hand, reactive oxygen species (ROS) are involved in the genesis of various cancer types by promoting oxidative DNA damage and deregulating gene expression [ 10 , 11 , 12 ]. Additionally, ROS can increase the invasive potential of malignant cells by inducing metalloproteinase gene expression [ 13 , 14 ].…”
The cancer-preventive agent Resveratrol (RSV) [3,5,4′-trihydroxytrans-stilbene] is a widely recognized antioxidant molecule with antitumoral potential against several types of cancers, including prostate, hepatic, breast, skin, colorectal, and pancreatic. Herein, we studied the effect of RSV on the cell viability and invasion potential of gastric cancer cells. AGS and MKN45 cells were treated with different doses of RSV (0–200 μM) for 24 h. Cell viability was determined using the Sulphorhodamine B dye (SRB) assay. For invasion assays, gastric cells were pre-treated with RSV (5–25 μM) for 24 h and then seeded in a Transwell chamber with coating Matrigel. The results obtained showed that RSV inhibited invasion potential in both cell lines. Moreover, to elucidate the mechanism implicated in this process, we analyzed the effects of RSV on SOD, heparanase, and NF-κB transcriptional activity. The results indicated that RSV increased SOD activity in a dose-dependent manner. Conversely, RSV significantly reduced the DNA-binding activity of NF-κB and the enzymatic activity of heparanase in similar conditions, which was determined using ELISA-like assays. In summary, these results show that RSV increases SOD activity but decreases NF-kB transcriptional activity and heparanase enzymatic activity, which correlates with the attenuation of invasion potential in gastric cancer cells. To our knowledge, no previous study has described the effect of RSV on heparanase activity. This article proposes that heparanase could be a key effector in the invasive events occurring during gastric cancer metastasis.
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