Reactive oxygen species a double-edged sword for mesothelioma

Our plain-English summary of Reactive oxygen species a double-edged sword for mesothelioma, by S. Benedetti, B. Nuvoli, S. Catalani, et al (Oncotarget, 2015).

The study

• Authors: S. Benedetti, B. Nuvoli, S. Catalani, R. Galati
• Journal: Oncotarget
• Published: 2015;6(19):16848-65
• Type of article: Review
• Cited by: 67 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

It is well known that oxidative stress can lead to chronic inflammation which, in turn, could mediate most chronic diseases including cancer. Oxidants have been implicated in the activity of crocidolite and amosite, the most powerful types of asbestos associated to the occurrence of mesothelioma. Currently rates of mesothelioma are rising and estimates indicate that the incidence of mesothelioma will peak within the next 10-15 years in the western world, while in Japan the peak is predicted not to occur until 40 years from now. Although the use of asbestos has been banned in many countries around the world, production of and the potentially hazardous exposure to asbestos is still present with locally high incidences of mesothelioma. Today a new man-made material, carbon nanotubes, has arisen as a concern; carbon nanotubes may display 'asbestos-like' pathogenicity with mesothelioma induction potential. Carbon nanotubes resulted in the greatest reactive oxygen species generation. How oxidative stress activates inflammatory pathways leading to the transformation of a normal cell to a tumor cell, to tumor cell survival, proliferation, invasion, angiogenesis, chemoresistance, and radioresistance, is the aim of this review.

In plain English

This was a review of research on reactive oxygen species (ROS), highly reactive oxygen-containing molecules, in malignant mesothelioma. It presented no new, fully described experiment, though the authors mentioned uncited preliminary data that a product called Cellfood increased ROS in mesothelioma cells. Asbestos was described as producing ROS through iron in the fibers and through activated inflammatory cells. They summarized laboratory, animal and human studies linking ROS to DNA damage, inflammation and tumor development. In one cited study, plasma malondialdehyde, a marker of oxidative damage, was higher in 97 asbestos-exposed workers than in 42 healthy male controls. The review also covered treatments acting partly through ROS, including radiation, cisplatin, pemetrexed and plant compounds tested in cells and mice. In one cited study, none of 9 patients given radiation alone responded, while 14 of 26 given radiation plus procarbazine responded subjectively or objectively, with tumor shrinkage only inside the radiation field. The authors concluded that ROS are involved in starting and advancing mesothelioma but are also used to kill cancer cells, so both pro-oxidant and antioxidant therapies were proposed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review of published laboratory, animal and human studies, with a brief mention of the authors' own uncited preliminary data
• Who was studied: No study population of its own. The authors reviewed published research on oxidative stress and malignant mesothelioma, including cell, animal and human studies.
• Exposure: Asbestos fibers and the ROS and reactive nitrogen species they generate. The fibers named were the amphiboles (crocidolite, amosite, anthophyllite, tremolite, actinolite) and chrysotile. ROS were described as coming from iron in the fibers and from activated inflammatory cells.
• Main results:
  • In a cited human study, plasma malondialdehyde (a marker of lipid peroxidation) was measured in 97 randomly selected asbestos-exposed workers and 42 healthy male controls. It was significantly higher in the exposed workers.
  • In a cited study, people who had been exposed to asbestos showed two to four times more DNA double-strand breaks in white blood cells than non-exposed people.
  • In a cited study, most malignant mesotheliomas showed strong expression of inducible nitric oxide synthase (iNOS), which was infrequent in non-neoplastic healthy mesothelium.
  • The review described cited evidence that human mesothelioma cell lines have increased Mn-SOD and catalase (antioxidant enzymes). The authors offered this as one explanation for why the cells resist oxidant-induced cell death.
  • In a cited study of 35 mesothelioma patients, none of the 9 treated with radiation alone responded. Of the 26 treated with procarbazine plus radiation, 14 responded subjectively or objectively.
  • In that same cited study, tumor shrinkage in the procarbazine-plus-radiation group was seen only within the radiation field.
  • In cited laboratory work, the green tea compound EGCG was more toxic to mesothelioma cells than to normal mesothelial cells, through a mechanism involving hydrogen peroxide and ROS.
  • The authors mentioned preliminary data, given without a citation, methods or numbers, that Cellfood increased ROS in mesothelioma cells at the doses used to kill them.
• The authors' conclusion: The authors concluded that ROS are involved in the initiation and progression of mesothelioma, but are also how non-surgical therapies kill cancer cells. Because of this 'double-edged' property, both pro-oxidant and antioxidant therapies have been proposed.
• Limitations the authors state:
  • The authors stated that, to their knowledge, no study had examined ROS production in mesothelioma cells treated with the pemetrexed and cisplatin combination.
  • The authors noted that, despite many preclinical studies, using resveratrol in patients is far from reality.
  • The authors noted that curcumin has limited bioavailability, which future studies must overcome.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Reactive Oxygen Species (ROS), Mesothelioma, Oxidative Stress, Chronic Inflammation, Crocidolite, Amosite, Angiogenesis.

Related studies

• Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles — A. Valavanidis, T. Vlachogianni, et al. (2009)
• Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung — D. Crouzier, S. Follot, et al. (2010)
• Inhibition of NADPH oxidase 4 induces apoptosis in malignant mesothelioma: Role of reactive oxygen species — M. Tanaka, Y. Miura, et al. (2015)
• Cytotoxicity and reactive oxygen species generation from aggregated carbon and carbonaceous nanoparticulate materials — K.M. Garza, K.F. Soto, et al. (2008)
• Integrated approach to immunotoxicity: electron transfer, reactive oxygen species, antioxidants, cell signaling, and receptors — P. Kovacic, R. Somanathan (2008)
• Pulmonary oxidative stress, inflammation and cancer: respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms — A. Valavanidis, T. Vlachogianni, et al. (2013)

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