Comparative Analysis of Cell Senescence Induced by the Chemotherapeutic Agents Doxorubicin, Cisplatin and Arsenic Trioxide in Human Myoblasts MB135

Abstract

Genotoxic and cytotoxic drugs, widely used in anticancer therapy, target proliferating cells and induce cell death through a variety of cell cycle-dependent mechanisms. The mechanisms of the delayed toxicity induced by chemotherapy are not fully understood. The accumulation of senescent cells may underlie some of the mechanisms for the development of late adverse effects of chemotherapy on muscle tissue. Cellular models are necessary for the development of therapeutic approaches to these side effects. In our study we used human immortalized myoblast MB135 to optimize the protocol for obtaining the senescent phenotype of muscle cells under the influence of chemotherapeutic drugs such as doxorubicin, cisplatin and arsenic trioxide (As₂O₃). We evaluated the dynamics of changes in senescence proteins pRb, p21 and p53 and SASP-associated proteins such as TNF, IL-1b, IL-6, IL-8, CXCL2, GDF15 using Western blot, RT-PCR and ELISA. Cell senescence was confirmed by the measurement of cell senescence index by flow cytometry after 7 days of exposure to chemotherapeutic agents. The obtained results indicate that all three investigated chemotherapeutic compounds induce the appearance of senescence markers, but the dynamics of these changes are somewhat different for them, which may reflect differences in the mechanisms of senescence phenotype induction.