Reactive oxygen species a double-edged sword for mesothelioma

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.

Keywords: cell proliferation; cell trasformation; mesothelioma; reactive oxygen species; therapy.

Figure 1. Link between ROS/RNS generation and cancer

High concentration of ROS and RNS, leading to oxidative stress and chronic inflammation, can cause macromolecule damage and cell injury that, in turn, activate signal transduction pathways linked to the progressive phases of carcinogenesis (cell transformation, cell proliferation, cell invasion and angiogenesis).

Figure 2. Asbestos-induced cell injury leading to mesothelioma

Mesothelial cells exposed to iron- and macrophage-mediated ROS/RNS production and inflammatory cytokines can cope cell injury and undergo malignant transformation giving rise to mesothelioma.

Figure 3. Cell signaling activation by asbestos

Exposure to asbestos fibers leads to the activation of downstream signaling cascades conducing to cell transformation, cancer cell survival and proliferation, angiogenesis and invasion.

Figure 4. Non-surgical strategies for mesothelioma treatment

Different types of mesothelioma treatment employ not only the standard protocols of chemiotherapy and radiotherapy, but also rely on phytochemicals and food supplements to induce cancer cell death.