Phenotype-dependent apoptosis signalling in mesothelioma cells after selenite exposure

Abstract

Background: Selenite is a promising anticancer agent which has been shown to induce apoptosis in malignant mesothelioma cells in a phenotype-dependent manner, where cells of the chemoresistant sarcomatoid phenotype are more sensitive.

Rat mesothelioma cell proliferation requires p38δ mitogen activated protein kinase and C/EBP-α

“…This observation is somehow contrarily to the function of C/EBP-␣ under different conditions and different cell types [43,44]. The observation might be explained by the fact that PMM cells can occur in two phenotypes, an epithelial-liked phenotype and a fibroblast-liked phenotype [45,46].…”

Variation in Drug Sensitivity of Malignant Mesothelioma Cell Lines with Substantial Effects of Selenite and Bortezomib, Highlights Need for Individualized Therapy

“…Consequently, doxorubicin (Meda AB, Solna, Sweden) was used at 1 µM, gemcitabine (Eli Lilly Sweden AB, Solna, Sweden) at 200 µM, carboplatin (Teva Sweden AB, Helsingborg, Sweden) at 100 µM, bortezomib (Janssen-Cilag AB, High Wycombe, Buckinghamshire, UK) at 1.3 µM and pemetrexed (Eli Lilly Sweden AB) at 90 µM. The concentration of selenite (Na 2 SeO 3 , 10 µM, Sigma-Aldrich) was chosen on the basis of previous studies and expected tolerable doses in vivo [10], [11].…”

“…Comparable results have been achieved in phase II studies using the combination of pemetrexed and carboplatin [15], as well as combining carboplatin, liposomized doxorubicin and gemcitabine [16]. We have previously reported strong phenotype-dependent effects of selenite and PSI, a proteasome inhibitor similar to bortezomib, on mesothelioma cells [9], [10], [11]. Others have shown promising results for selenite in early clinical trials in different human tumor types [17], [18].…”

“…Our previous studies have indicated a phenotype-dependent sensitivity to experimental drugs or chemotherapeutic agents which are known to target these systems [9], [10], [11]. Differentiation related sensitivity profiles correlate to clinical findings, and patients with a tumor dominated by the sarcomatoid phenotype accordingly have a worse prognosis [4].…”

“…We included two experimental drugs: selenite and bortezomib. Selenite is a modulator of the redox system, and we further investigated its phenotype-dependent effect and potential synergistic effects with other drugs [10], [11]. We evaluated the effect of bortezomib, a proteasome inhibitor that has been demonstrated to be cytotoxic on mesothelioma cells [9], [19], [20].…”