Platinum-based chemotherapy induces demyelination of Schwann cells in oral squamous cell carcinoma treatment.

BACKGROUND: Cisplatin, carboplatin, and oxaliplatin are the only three platinum-based antineoplastic drugs that have been accepted worldwide for treating various cancers. Up to 83.6% of patients treated with platinum-based antineoplastic drugs will develop chemotherapy-induced peripheral neuropathy (CIPN), manifesting as sensory paresthesias, dysesthesias, and hypoesthesias that can cause significant adverse impact to daily activities. AIM: To investigate how these three platinum-based drugs affect mitochondrial function and myelination state of Schwann cells and the signalling pathway involved. METHOD: 2 muM Cisplatin, 20 muM carboplatin, and 1 muM oxaliplatin were used to inhibit the growth of CAL-27 by 20% respectively. These drugs were then used to induce chemotherapy-induced peripheral neuropathy in Rat Schwann Cells (RSC96). The changes in cell metabolism and myelin formation in RSC96 were investigated. RESULT: Cisplatin and carboplatin, but not oxaliplatin increased intracellular and mitochondrial reactive oxygen species in RSC96. Only Cisplatin and carboplatin decreased mitochondrial membrane potential (DeltaPsim) and ATP production in RSC96. Both Cisplatin and carboplatin led to demyelination of RSC96, characterized by increased expression of p75(NTR) and decreased expression of myelin protein zero (MPZ). CONCLUSION: Cisplatin and carboplatin, but not oxaliplatin, caused mitochondrial dysfunction and induced demyelination in RSC96 while showing similar toxicity to head and neck cancer cells. Oxaliplatin may be a potential chemotherapy drug to prevent CIPN in patients with head and neck cancer.