A Paradoxical Role for Eicosanoids: Radioprotectants and Radiosensitizers

Walden, Thomas L.

doi:10.1007/978-1-4684-5457-4_28

Cited by 11 publications

(6 citation statements)

References 28 publications

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“…Lipid peroxidation is an important event related to cell death, and has been reported to cause severe impairment of membrane functions through increased membrane permeability and membrane protein oxidation, DNA damage, cyto-toxicity and eventually cell death [57-60]. It has been indicated that the hydroxyl radical is the most active species involved in radiation induced LPO [61,62]. The increase of LPO byproduct (i.e., malondialdehyde) following radiation exposure as revealed in the present study is a clear indication of the increased oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Management of Radiation Injuries by Panax ginseng Extract

Verma¹,

Jahan²,

Kim³

et al. 2011

Journal of Ginseng Research

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Chemical radiation protection is an important strategy to protect living beings against the deleterious effects of radiation. In the present study, the radioprotective effect of hydro-alcoholic extract of Panax ginseng extract (PGR-HAE) was studied on radiation-induced deleterious alterations in Swiss albino mice. Oral administration of such extract (25 mg/kg b wt/day/animal) for 5 consecutive days, half an h. before whole-body exposure to 6 Gy gamma radiation, enhanced the 30 days survival and also inhibited the radiogenic sickness, weight loss and life shortening. PGR-HAE ameliorated radiation induced depletion in blood constituents at different necropsy intervals between 12 h to 30 d, and significantly increased the number of femoral spleen colony forming units that survived after irradiation. Furthermore, it checked depletion of glutathione and antioxidant enzymes (superoxide dismutase, catalase, and glutathione S-transferase) as well as elevation of lipid peroxidation (LPO) level in blood and liver. The significant reduction in the yield of LPO demonstrates that PGR-HAE protects the membranes against radiation-induced oxidative damage. These findings conclude that such plant extract provides significant radioprotection, and it may be potentially valuable in the prevention of injuries caused during planned and unplanned radiation exposure.

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Section: Discussionmentioning

confidence: 99%

Management of Radiation Injuries by Panax ginseng Extract

Verma¹,

Jahan²,

Kim³

et al. 2011

Journal of Ginseng Research

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“…It has been reported that radiation causes lipid peroxidation in cells, in addition to its widely known ability to induce DNA damage. Thus, we hypothesized that cell death caused by radiation alone may partially be due to ferroptosis, particularly in contexts in which DNA damage does not induce apoptosis.…”

Section: Results and Discussionmentioning

confidence: 99%

“…This genotoxicity leads to downstream effects such as apoptosis and mitotic catastrophe, which are thought to be the predominant mechanisms of cancer cell death following irradiation . Nevertheless, some prior reports have highlighted the capacity for radiation to produce hydroxyl radicals and even lipid peroxidation in cell membranes. , With the framework of ferroptosis, a lipid-peroxidation-based form of regulated cell death that can be modulated by a wide arsenal of pharmacological agents and metabolic interventions, it may now be possible to enhance the radiation-induced lipid damage response to kill tumors. This alternative mechanism may be especially effective in tumors with either intrinsic or acquired resistance to the genotoxic effects of radiation, such as those with increased capacity for DNA repair or a defective apoptosis pathway.…”

Section: Results and Discussionmentioning

confidence: 99%

“…In addition to DNA damage, radiation also generates reactive oxygen species, which can result in oxidation of biomolecules, such as lipid oxidation . While this effect has largely remained unexplored, a phospholipid-peroxidation-driven form of regulated cell death, ferroptosis, has recently been identified, and increasing evidence has been found to support its importance in a variety of biological and disease processes .…”

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confidence: 99%

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Radiation-Induced Lipid Peroxidation Triggers Ferroptosis and Synergizes with Ferroptosis Inducers

et al. 2020

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Although radiation is widely used to treat cancers, resistance mechanisms often develop and involve activation of DNA repair and inhibition of apoptosis. Therefore, compounds that sensitize cancer cells to radiation via alternative cell death pathways are valuable. We report here that ferroptosis, a form of nonapoptotic cell death driven by lipid peroxidation, is partly responsible for radiation-induced cancer cell death. Moreover, we found that small molecules activating ferroptosis through system xc – inhibition or GPX4 inhibition synergize with radiation to induce ferroptosis in several cancer types by enhancing cytoplasmic lipid peroxidation but not increasing DNA damage or caspase activation. Ferroptosis inducers synergized with cytoplasmic irradiation, but not nuclear irradiation. Finally, administration of ferroptosis inducers enhanced the antitumor effect of radiation in a murine xenograft model and in human patient-derived models of lung adenocarcinoma and glioma. These results suggest that ferroptosis inducers may be effective radiosensitizers that can expand the efficacy and range of indications for radiation therapy.

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“…It has been reported that the mechanisms of radiation resistance involve inhibition of apoptosis [ 79 ], or alterations in DNA repair pathways [ 80 ], or processes inducing necroptosis, and autophagy [ 81 , 82 ]. Therefore, mechanisms for strategies to study radioresistant tumors are essential, but besides DNA damage, radiation also generates reactive oxygen species (ROS) which can cause the oxidation of biomolecules, such as lipid oxidation [ 83 ]. It has also been hypothesized that inefficacy of radiation can be due to the process known as ferroptosis and that inducers of such a process may be effective radiosensitizers that can expand the efficacy for radiation therapy [ 84 ].…”

Section: Radiation and Its Biological Effectsmentioning

confidence: 99%

Gene Signatures Induced by Ionizing Radiation as Prognostic Tools in an In Vitro Experimental Breast Cancer Model

Calaf

Crispin

Roy

et al. 2021

Cancers

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This study aimed to analyze the expression of genes involved in radiation, using an Affymetrix system with an in vitro experimental breast cancer model developed by the combined treatment of low doses of high linear energy transfer (LET) radiation α particle radiation and estrogen yielding different stages in a malignantly transformed breast cancer cell model called Alpha model. Altered expression of different molecules was detected in the non-tumorigenic Alpha3, a malignant cell line transformed only by radiation and originally derived from the parental MCF-10F human cell line; that was compared with the Alpha 5 cell line, another cell line exposed to radiation and subsequently grown in the presence 17β-estradiol. This Alpha5, a tumorigenic cell line, originated the Tumor2 cell line. It can be summarized that the Alpha 3 cell line was characterized by greater gene expression of ATM and IL7R than control, Alpha5, and Tumor2 cell lines, it presented higher selenoprotein gene expression than control and Tumor2; epsin 3 gene expression was higher than control; stefin A gene expression was higher than Alpha5; and metallothionein was higher than control and Tumor2 cell line. Therefore, radiation, independently of estrogen, induced increased ATM, IL7R, selenoprotein, GABA receptor, epsin, stefin, and metallothioneins gene expression in comparison with the control. Results showed important findings of genes involved in cancers of the breast, lung, nervous system, and others. Most genes analyzed in these studies can be used for new prognostic tools and future therapies since they affect cancer progression and metastasis. Most of all, it was revealed that in the Alpha model, a breast cancer model developed by the authors, the cell line transformed only by radiation, independently of estrogen, was characterized by greater gene expression than other cell lines. Understanding the effect of radiotherapy in different cells will help us improve the clinical outcome of radiotherapies. Thus, gene signature has been demonstrated to be specific to tumor types, hence cell-dependency must be considered in future treatment planning. Molecular and clinical features affect the results of radiotherapy. Thus, using gene technology and molecular information is possible to improve therapies and reduction of side effects while providing new insights into breast cancer-related fields.

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A Paradoxical Role for Eicosanoids: Radioprotectants and Radiosensitizers

Cited by 11 publications

References 28 publications

Management of Radiation Injuries by Panax ginseng Extract

Management of Radiation Injuries by Panax ginseng Extract

Radiation-Induced Lipid Peroxidation Triggers Ferroptosis and Synergizes with Ferroptosis Inducers

Gene Signatures Induced by Ionizing Radiation as Prognostic Tools in an In Vitro Experimental Breast Cancer Model

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