Abstract
Significance:
Cisplatin is an important component of treatment regimens for different cancers. Notwithstanding that therapeutic success often results from partial efficacy or stabilizing the disease, chemotherapy failure is driven by resistance to drug treatment and occurrence of side effects, such as progressive irreversible ototoxicity. Cisplatin's side effects, including ototoxicity, are often dose-limiting. Recent Advances: Cisplatin ototoxicity results from several mechanisms, including: redox imbalance caused by reactive oxygen species (ROS) production and lipid peroxidation, activation of inflammation, p53 and its downstream pathways that culminate in apoptosis. Considerable efforts in research have targeted development of molecular interventions that can be concurrently administered with cisplatin or other chemotherapies in order to reduce side effect toxicities while preserving or enhancing the anti-neoplastic effects. Evidence from studies has indicated some polyphenols, such as curcumin, can help to regulate redox signaling and inflammatory effects. Furthermore, polyphenols can exert opposing effects in different types of tissues, i.e. normal cells undergoing stressful conditions versus cancer cells.
Critical issues:
This review article summarizes evidence of curcumin antioxidant effect against cisplatin-induced ototoxicity that is converted to a pro-oxidant activity in cisplatin-treated cancer cells, thus providing an ideal chemosensitivity combined with otoprotection. Polyphenols can modulate the adaptive responses to stress in the cisplatin-exposed cochlea. These adaptive effects can result from the interaction/crosstalk between the cell's defenses, inflammatory molecules, and the key signaling molecules of STAT-3, NF-κB, p53, and Nrf-2.
Future directions:
We provide molecular evidence for alternative strategies for chemotherapy with cisplatin addressing the otoprotection and chemosensitization properties of polyphenols.
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