TY - JOUR
T1 - Antitumor activity of selenium compounds and its underlying mechanism in human oral squamous cell carcinoma cells
T2 - A preliminary study
AU - Endo, Manabu
AU - Hasegawa, Hiroshi
AU - Kaneko, Tetsuharu
AU - Kanno, Chihiro
AU - Monma, Tsutomu
AU - Kano, Makoto
AU - Shinohara, Fumiaki
AU - Takahashi, Tetsu
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Objective Oral cancer is an aggressive disease that infiltrates the adjacent tissues and frequently metastasizes to lymph nodes in the neck. Currently, no chemotherapy effectively prevents its metastasis. Selenium compounds have been recently scrutinized as chemotherapeutic agents for various cancers. In this study, we aimed to investigate the antitumor activity of selenium compounds and elucidate the underlying inhibitory mechanism of these agents in oral cancer cells. Methods The growth inhibitory effects of selenium compounds (sodium selenite, selenomethionine, and Se-methylselenocysteine) on human oral squamous cell carcinoma (HOSCC) cell lines (HSC-3, HSC-4, and SAS) were evaluated by MTT assay. Selenite-induced apoptosis, caspase activity, and endoplasmic reticulum (ER) stress in HSC-3 cells were evaluated by flow cytometry and western blot. Effects of selenite on Akt expression in HSC-3 cells were evaluated by ELISA and western blot. Results Selenium compounds significantly inhibited cell growth and induced apoptosis in HOSCC cell lines. HSC-3 cells, in particular, were highly sensitive to selenite. In selenite-treated HSC-3 cells, caspase-3, 8, and 9 were conspicuously activated; pretreatment with pan-caspase inhibitor or caspase-12 inhibitor dramatically reduced selenite-induced apoptosis; ER stress markers, caspase-12 and eIF-2α, were highly activated, but Akt activation in the Akt/phosphoinositide-3-kinase pathway was downregulated. Conclusion Our findings indicate that selenite induces apoptosis in HOSCC cell lines in a caspase-dependent manner through mitochondrial, death-receptor, and ER stress pathways. In addition, selenite could exhibit antitumor activity by downregulating Akt activation, which plays an important role in cell growth and chemotherapy resistance.
AB - Objective Oral cancer is an aggressive disease that infiltrates the adjacent tissues and frequently metastasizes to lymph nodes in the neck. Currently, no chemotherapy effectively prevents its metastasis. Selenium compounds have been recently scrutinized as chemotherapeutic agents for various cancers. In this study, we aimed to investigate the antitumor activity of selenium compounds and elucidate the underlying inhibitory mechanism of these agents in oral cancer cells. Methods The growth inhibitory effects of selenium compounds (sodium selenite, selenomethionine, and Se-methylselenocysteine) on human oral squamous cell carcinoma (HOSCC) cell lines (HSC-3, HSC-4, and SAS) were evaluated by MTT assay. Selenite-induced apoptosis, caspase activity, and endoplasmic reticulum (ER) stress in HSC-3 cells were evaluated by flow cytometry and western blot. Effects of selenite on Akt expression in HSC-3 cells were evaluated by ELISA and western blot. Results Selenium compounds significantly inhibited cell growth and induced apoptosis in HOSCC cell lines. HSC-3 cells, in particular, were highly sensitive to selenite. In selenite-treated HSC-3 cells, caspase-3, 8, and 9 were conspicuously activated; pretreatment with pan-caspase inhibitor or caspase-12 inhibitor dramatically reduced selenite-induced apoptosis; ER stress markers, caspase-12 and eIF-2α, were highly activated, but Akt activation in the Akt/phosphoinositide-3-kinase pathway was downregulated. Conclusion Our findings indicate that selenite induces apoptosis in HOSCC cell lines in a caspase-dependent manner through mitochondrial, death-receptor, and ER stress pathways. In addition, selenite could exhibit antitumor activity by downregulating Akt activation, which plays an important role in cell growth and chemotherapy resistance.
KW - Akt pathway
KW - Apoptosis
KW - Endoplasmic reticulum stress
KW - Selenium compounds
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U2 - 10.1016/j.ajoms.2016.08.006
DO - 10.1016/j.ajoms.2016.08.006
M3 - Article
AN - SCOPUS:84994476347
VL - 29
SP - 17
EP - 23
JO - Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
JF - Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
SN - 2212-5558
IS - 1
ER -