Capsaicin Induces Apoptosis of Cisplatin-Resistant Stomach Cancer Cells by Causing Degradation of Cisplatin-Inducible Aurora-A Protein

Abstract

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.

Capsaicin Mediates Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells via Stabilizing and Activating p53

“…Except aforementioned therapeutic value, several studies also have demonstrated that capsaicin could be functioned as a chemopreventive and chemotherapeutic agent in different human cancer models. As reported, capsaicin decreased the growth of human leukemic cells 6, gastric 7, nasopharyngeal 8, prostate 9, and hepatic carcinoma cells 10 in vitro because of its ability to mediate cell cycle arrest and induce cell apoptosis. However, the molecular mechanism underlying capsaicin-induced growth inhibition and apoptosis was not exhaustively elucidated.…”

Potential Phytopharmacy and Food Applications of Capsicum spp.: A Comprehensive Review

“…In human gastric cell lines, capsaicin induces cell death via bcl-2-sensitive apoptotic pathway [104], overexpression of p53 and/or c-myc genes [107], activation of caspase-3 [108], and inhibits cell proliferation by cytochrome c release [105]. Moreover, capsaicin enhances the potential effectiveness of other chemotherapeutic agents on Korean human gastric cancer cell line, increasing apoptotic cell death of cisplatin-resistant gastric cancer cells after co-treatment with cisplatin [109]. In human colorectal cancer cells in vitro, capsaicin suppressed cell proliferation involving the suppression of transcriptional activity of β-catenin [106].…”

Capsaicin synergizes with camptothecin to induce increased apoptosis in human small cell lung cancers via the calpain pathway

“…Monofunctional platinum-based drugs, like LH5, showed increased apoptotic activity in combination with capsaicin [10]. Similarly, the treatment of stomach cancer cells with a combination of cisplatin and capsaicin caused greater than apoptosis than either of these agents given singly [11, 12]. A similar effect was also observed when capsaicin was given in combination with the doxorubicin analog pirarubicin [13].…”