Capsaicin Potentiates Anticancer Drug Efficacy Through Autophagy-Mediated Ribophorin II Downregulation and Necroptosis in Oral Squamous Cell Carcinoma Cells

Frontiers in Pharmacology

Chiung-Hua Wung¹  Kai-Li Liu²  Tien-Ming Yuan⁴  Show-Mei Chuang⁵  Yi-Ching Huang⁵  Bang-Hung Liu⁵ 

[1] Biotechnology Center, National Chung Hsing University, Taichung, Taiwan;Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan;Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan;Department of Surgery, Feng Yuan Hospital, Ministry of Health and Welfare, Taichung, Taiwan;Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan;

关键词: capsaicin;    ribophorin II;    autophagy;    apoptosis;    necroptosis;    DNA damage;   

DOI  :  10.3389/fphar.2021.676813

来源: DOAJ

【 摘 要 】

The ability of capsaicin co-treatment to sensitize cancer cells to anticancer drugs has been widely documented, but the detailed underlying mechanisms remain unknown. In addition, the role of ribophorin II turnover on chemosensitization is still uncertain. Here, we investigated capsaicin-induced sensitization to chemotherapeutic agents in the human oral squamous carcinoma cell lines, HSC-3 and SAS. We found that capsaicin (200 μM) did not induce remarkable apoptotic cell death in these cell lines; instead, it significantly enhanced autophagy with a concomitant decrease of ribophorin II protein. This capsaicin-induced decrease in ribophorin II was intensified by the autophagy inducer, rapamycin, but attenuated by the autophagy inhibitors, ULK1 inhibitor and chloroquine, indicating that the autophagic process was responsible for the capsaicin-induced down-regulation of ribophorin II. Co-administration of capsaicin with conventional anticancer agents did, indeed, sensitize the cancer cells to these agents. In co-treated cells, the induction of apoptosis was significantly reduced and the levels of the necroptosis markers, phospho-MLKL and phospho-RIP3, were increased relative to the levels seen in capsaicin treatment alone. The levels of DNA damage response markers were also diminished by co-treatment. Collectively, our results reveal a novel mechanism by which capsaicin sensitizes oral cancer cells to anticancer drugs through the up-regulation of autophagy and down-regulation of ribophorin II, and further indicate that the induction of necroptosis is a critical factor in the capsaicin-mediated chemosensitization of oral squamous carcinoma cells to conventional anticancer drugs.

【 授权许可】

Unknown