Molecular Mechanisms of redox-active cerium oxide nanoparticles in inhibition of tumor progression

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Our data show that the anticancer effect of cerium oxide nanoparticles (CNP) can be enhanced by a combination with classical chemotherapeutics such as doxorubicin, in parallel having no damaging effect on non-tumorigenic cells. In addition, the dose of the chemotherapeutical drug can be lowered in a combination with CNP to decrease the harmful effect on healthy (non-tumorigenic)) cells, but without changing the anticancer effect on tumor cells. That leads to the following main objectives of the planned project:Studies on the molecular mechanims of cerium oxide nanoparticles to inhibit tumor progression and validation of their application in a combinational approach with doxorubicin.In the planned project, the molecular effects of CNP alone or in combination with doxorubicin will be studied on tumor and healthy (non-tumorigenic) cells to evaluate the potential use and/or risk of CNP as a molecular tool in an anticancer therapy and to increase the efficacy of a potential combination therapy. On the one hand, we want to have a detailed look on the mitochondrial dynamics/quality control as well as mitophagy/autophagy after treatment the different cell types cells with CNP and/or doxorubicin. On the other hand, the effect of CNP and doxorubicin alone or in combination on the thiol modification of the cysteine proteome and its functional consequence will be studied on tumor and non-tumorigenic cells to determine redox targets for future therapeutical approaches.