Carboplatin Elicits ROS Responses and Potentially Regulates Translation Program in Cancer Systems

ABSTRACT

Platinum‐based chemotherapeutic agents display broad‐spectrum and high anticancer activity, the primary target of which is nuclear DNA. During platinum chemotherapeutics, the steady‐state levels of reactive oxygen species (ROS) are generally elevated. However, the pathways by which platinum drugs generate ROS and the biological responses still lack systematic studies. Taking carboplatin as an example, we found that both ROS and antioxidant enzyme expression were elevated, and multiple genes for mitochondrial translation and respiration were up‐regulated to serve as contributors to ROS. Various genes for mitoribosome stress were also up‐regulated, potentially controlling mitochondrial respiration and translation. The expression of single‑stranded DNA‑binding protein 1 ( SSBP1 ), a mitochondrial translational regulator and a potential anti‑cancer target, was up‑regulated in carboplatin‐treated cancer cells and in 22 tumor tissues, probably influencing the efficacy of chemotherapy. The potential crosstalk between mitochondrial translation and ROS response should be crucial for the clinical use of platinum drugs.