Antitumor activity of selenium compounds and its underlying mechanism in human oral squamous cell carcinoma cells: A preliminary study

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• 作者：Manabu Endo^a ; ^b ; Hiroshi Hasegawa^a ; ^{hi612hasegawa@gmail.com} ; Tetsuharu Kaneko^a ; Chihiro Kanno^a ; Tsutomu Monma^c ; Makoto Kano^d ; Fumiaki Shinohara^e ; Tetsu Takahashi^b
• 关键词：Selenium compounds ; Apoptosis ; Endoplasmic reticulum stress ; Akt pathway
• 刊名：Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：29
• 期：1
• 页码：17-23
• 全文大小：1057 K
• 卷排序：29

文摘

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.MethodsThe 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.ResultsSelenium 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.ConclusionOur 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.