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Nanotechnology-Mediated Radiation Therapy
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
In the majority of the radiation-based cancer therapies, apoptosis takes the spotlight in causing cell death mechanisms; however, newer reports have started coming out to shift the focus toward whether cancer therapies can also induce other forms of cell death. In a study carried out by Lei G et al. demonstrated the link between ionizing radiation and a form of regulated cell death caused by lipid peroxidation called ferroptosis [58]. The authors analyzed that ionizing radiation in cancer cells led to the induction of reactive oxygen species (ROS) and upregulated expression of a lipid metabolizing enzyme ACSL4 to initiate ferroptosis. The study concluded that ferroptosis in cancer patients conferred better response and survival to radiotherapy.
Cell death after irradiation: How, when and why cells die
Published in Michael C. Joiner, Albert J. van der Kogel, Basic Clinical Radiobiology, 2018
There is strong evidence that necrosis can also occur in a ‘programmed’ manner and constitute an alternative to apoptosis. Necroptosis refers to a specific form of programmed necrosis that is initiated by receptor-interacting protein kinase 3 (RIPK3) and other forms of programmed necrosis include the excitotoxicity of neurons. For example, induction of necrosis is dependent on cellular energy stores, such as NAD and ATP, and can be regulated by receptor signalling pathways. Furthermore, cell stress and cell signalling including oxidative stress, calcium levels and p53 activation have been shown to influence lysosomal membrane permeability. Permeabilization leads to intracellular acidification and release of various enzymes that can promote necrosis. Other distinct forms of non-apoptotic cell death that result from aberrant cell signalling have been identified. For example, ferroptosis is an iron-linked form of cell death that occurs when cells are unable to control iron-dependent reactive oxygen species generation. Although it is not clear how the cell controls necrosis, ferroptosis or other direct forms of programmed cell death following irradiation, the frequency with which this is observed varies among different cell types. This suggests that, just as for all the other forms of cell death, cellular pathways control the sensitivity of its activation.
Applications of Antiviral Nanoparticles in Cancer Therapy
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Anusha Konatala, Sai Brahma Penugonda, Fain Parackel, Sudhakar Pola
In a fascinating study conducted by Ou et al. (2017), low density lipoprotein NPs were conjugated with docosahexaenoic acid (LDL-DHA), and their anticancer activity was measured. They described a novel anti-apoptotic iron-mediated cell-death pathway called ferroptosis, caused by the LDL-DHA AVNPs through which rat and human HCC cell lines were killed. Three features that stood out in this cell-death pathway were the lipid peroxidation, depletion of glutathione, and the inactivation of the lipid antioxidant glutathione peroxidase (GPX4). In an extension of their in vitro study, the group also studied the in vivo effect of LDL-DHA on tumour xenografts in mice and found that the intratumoral injections inhibited the growth of HCC long-term and caused ferroptic cell death. In a study to understand the therapeutic potential of, and to create an efficient delivery system for, umbelliferone β-D-galactopyranoside (UFG), Wistar rats with diethyl nitrosamine (DEN)-induced HCC were investigated in vivo, and HuH-7 and Hep-G2 were investigated in vitro. The group experimented with a PLGA NP-based delivery system prepared and loaded with UFG through sonication. DEN-induced reactive oxygen species generation, mitochondrial dysfunction, and pro-inflammatory cytokine alteration were used to characterise the anticancer potential of UFG-PLGA-NPs. In a similar study by a group of researchers, rutin-loaded PLGA NPs were assessed for their anticancer activity in in vitro, in vivo, and biochemical studies. They found that the RT-PLGA-NPs administered orally reduced the incidence of hepatic nodules and exhibited significant anticancer activity.
PGRMC1 promotes triple-negative breast cancer cell growth via suppressing ferroptosis
Published in Climacteric, 2023
Y. Zhao, X. Ruan, J. Cheng, X. Xu, M. Gu, A. O. Mueck
Ferroptosis was firstly coined in 2012, defining a new form of programmed cell death induced by the small molecule Erastin, which inhibits the import of cystine, leading to lipid peroxidation and cell death by depletion of glutathione and of the GPX4 inactivation [14]. Metabolic pathways controlling amino acid and glutathione metabolism, lipid metabolism and iron metabolism pathways have been well characterized to affect ferroptosis in different ways [24]. Furthermore, a substantial gene has also been reported to regulate ferroptosis. PGRMC1 has been well known for its roles in metabolism and heme binding, predicting potential regulatory roles in ferroptosis, which was further proved in our present study, demonstrated in three possible ways. Firstly, positive correlation between PGRMC1 and glutathione metabolism was observed in TNBC patients, suggesting that higher PGRMC1 expression might increase the glutathione levels to antagonize ferroptosis in TNBC cells. However, how the expression of PGRMC1 affects the glutathione metabolism pathway genes’ expression remains to be explored, which might be due either to indirect effects at the transcript level or mRNA stability and properly related to the hormone effect, as PGRMC1 is a hormone receptor. Secondly, PGRMC1 might suppress ferroptosis through binding heme and thus decrease the oxidative form of iron. Lastly, expression of ferroptosis-related genes might be regulated by PGRMC1 expression in breast cancer cells.
Ferritinophagy was involved in long-term SiNPs exposure induced ferroptosis and liver fibrosis
Published in Nanotoxicology, 2023
Qingqing Liang, Yuexiao Ma, Fenghong Wang, Mengqi Sun, Lisen Lin, Tianyu Li, Junchao Duan, Zhiwei Sun
Normal hepatocyte death is the core factor leading to hepatic fibrosis (Yoon, Friedman, and Lee 2016). Ferroptosis is a regulated form of cell death characterized by iron-dependent lipid peroxidation (Dixon et al. 2012). Redox active iron and glutathione peroxidase 4 (GPX4) participates in the initiation and repair of lipid peroxidation mediated by free radicals, respectively (Yu et al. 2022). Failure to repair lipid peroxidation further leads to membrane permeability and cell death (Dixon and Stockwell 2019). Nanoparticles have been proved to evoke ferroptosis in cancer cells and hippocampal neurons (Qin et al. 2020; Kim et al. 2016; Zhang et al. 2021). Both basic and clinical studies have illustrated that ferroptosis features prominently in many liver diseases (Xie et al. 2016). However, few studies have focused on ferroptosis in hepatocytes caused by nanoparticles.
A novel treatment strategy to prevent Parkinson’s disease: focus on iron regulatory protein 1 (IRP1)
Published in International Journal of Neuroscience, 2023
Thomas M. Berry, Ahmed A. Moustafa
Iron levels are high is brains of patients with PD. The conclusion that has been drawn is that iron is toxic in PD and that iron levels must be decreased by iron chelators. This paper holds that iron utilization is dysregulated in PD due to dysregulation of IRP1. In terms of treatment of PD ‘iron is toxic’ in PD is much different than ‘iron utilization is dysregulated’ in PD. Iron decreases levels of IRP1. By tightly controlling iron absorption via iron from iron carbonyl given by gavage three times a day IRP1 levels can be tightly controlled with iron utilization tightly controlled. Research on ferroptosis has been undertaken by in vitro methods where ferroptosis is increased when iron is added to cell cultures. This article holds that in vivo enteral supplementation of iron would have a much different effects, stopping ferroptosis and preventing PD. Paradoxically to stop ferroptosis supplementation with iron could be required.