Capsaicin induces apoptosis of cisplatin-resistant stomach cancer cells by causing degradation of cisplatin-inducible Aurora-A protein.

Various chemotherapeutic agents such as cisplatin have been used to treat gastric cancer. However, a substantial number of patients acquire resistance to this treatment, and this is followed by rapid relapse of the disease. We investigated the anticancer effect of capsaicin, the active ingredient in red pepper, in the cisplatin-resistant Korean human gastric cancer cell line SNU-668. We found that treatment of SNU-668 cells with capsaicin in combination with cisplatin induced higher apoptotic cell death than that of treatment with either capsaicin or cisplatin alone. Furthermore, we discovered that Aurora-A protein increased in response to cisplatin and was degraded upon combined treatment with capsaicin with cisplatin, suggesting that the Aurora-A-mediated signaling pathway is responsible for the resistance to cisplatin in cisplatin-resistant gastric cancer cell lines. Combined treatment with capsaicin and cisplatin induced G1/S arrest, whereas cisplatin alone caused accumulation in G2/M. Combined treatment with capsaicin and cisplatin inhibited IκB phosphorylation in a dose-dependent manner, suggesting that Aurora-A directly or indirectly regulates NF-κB translocation. We propose that combined administration of cisplatin and capsaicin may provide a strategy for overcoming cisplatin resistance.