Combination of Conventional Chemotherapeutics with Redox-Active Cerium Oxide Nanoparticles-A Novel Aspect in Cancer Therapy

    Authors

    M. Sack; L. Alili; E. Karaman; S. Das; A. Gupta; S. Seal;P. Brenneisen

    Comments

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    Abbreviated Journal Title

    Mol. Cancer Ther.

    Keywords

    OXIDATIVE STRESS; MALIGNANT-MELANOMA; DRUG-DELIVERY; TUMOR-CELLS; DNA-DAMAGE; IN-VITRO; DOXORUBICIN; NANOCERIA; RADIATION; TOXICITY; Oncology

    Abstract

    Nanotechnology is becoming an important field of biomedical and clinical research and the application of nanoparticles in disease may offer promising advances in treatment of many diseases, especially cancer. Malignant melanoma is one of the most aggressive forms of cancer and its incidence is rapidly increasing. Redox-active cerium oxide nanoparticles (CNP) are known to exhibit significant antitumor activity in cells derived from human skin tumors in vitro and in vivo, whereas CNP is nontoxic and beyond that even protective (antioxidative) in normal, healthy cells of the skin. As the application of conventional chemotherapeutics is associated with harmful side effects on healthy cells and tissues, the clinical use is restricted. In this study, we addressed the question of whether CNP supplement a classical chemotherapy, thereby enhancing its efficiency without additional damage to normal cells. The anthracycline doxorubicin, one of the most effective cancer drugs, was chosen as reference for a classical chemotherapeutic agent in this study. Herein, we show that CNP enhance the antitumor activity of doxorubicin in human melanoma cells. Synergistic effects on cytotoxicity, reactive oxygen species generation, and oxidative damage in tumor cells were observed after co-incubation. In contrast to doxorubicin, CNP do not cause DNA damage and even protect human dermal fibroblasts from doxorubicin-induced cytotoxicity. A combination of classical chemotherapeutics with nongenotoxic but antitumor active CNP may provide a new strategy against cancer by improving therapeutic outcome and benefit for patients. (C) 2014 AACR.

    Journal Title

    Molecular Cancer Therapeutics

    Volume

    13

    Issue/Number

    7

    Publication Date

    1-1-2014

    Document Type

    Article

    Language

    English

    First Page

    1740

    Last Page

    1749

    WOS Identifier

    WOS:000338710100006

    ISSN

    1535-7163

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