Capsaicin Modulates DNA Damage Related Gene Expressions in Cisplatin-Induced Ototoxicity

Cisplatin (CDDP) is a potent anticancer agent with significant side effects, including ototoxicity. Capsaicin (CAPS), the active compound in chili peppers, has shown protective effects against CDDP-induced toxicities. This study aimed to investigate the role of capsaicin in CDDP-induced ototoxicity via DNA damage and apoptotic cell death pathways in House Ear Institute Organ of Corti 1 (HEI-OC1) cells and to evaluate its effects on neuroblastoma (KELLY) cells under the same conditions.

HEI-OC1 and KELLY neuroblastoma cells were treated with CDDP (100 μM), CAPS (5 μM), and CAPS+CDDP combinations for 24 h. Cell viability was assessed using the WST-1 assay, and apoptosis was evaluated by Annexin V/PI flow cytometry. DNA damage-related gene expressions were analyzed in HEI-OC1 cells using a real-time PCR array. CAPS alone did not alter the viability of HEI-OC1 or KELLY cells. CDDP significantly reduced the viability of both.

CAPS + CDDP combination significantly decreased KELLY cell viability, while only slightly affecting HEI-OC1 cells. Both CDDP alone and CAPS + CDDP induced similar levels of apoptosis in HEI-OC1 cells. In KELLY cells, the combination induced greater apoptosis than CDDP alone. CDDP treatment upregulated DNA damage-related genes and downregulated DNA repair genes in HEI-OC1 cells. CAPS + CDDP treatment altered expression profiles, suggesting a role in DNA repair modulation.

Capsaicin may serve as a moderate protective agent against cisplatin-induced ototoxicity without compromising cisplatin's cytotoxic effects on neuroblastoma cells. Changes in DNA repair-related gene expression support capsaicin's involvement in modulating the cellular response to cisplatin.