Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Japan.
Department of Otolaryngology Head and Neck Surgery, Mie University Graduate School of Medicine, Tsu, Japan.
Amino Acids. 2018 Dec;50(12):1749-1758. doi: 10.1007/s00726-018-2651-2. Epub 2018 Sep 17.
Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck malignancy with a high incidence in southern China. Previous studies have confirmed that taurine shows an anti-cancer effect on a variety of human tumors by inhibiting cell proliferation and inducing apoptosis. However, the underlying molecular mechanism of its anti-cancer effect on NPC is not well understood. To clarify these anti-cancer mechanisms, we performed cell viability and colony formation assays. Apoptotic cells were quantified by flow cytometry. The expression levels of apoptosis-related proteins were evaluated by Western blot. The results showed that taurine markedly inhibited cell proliferation in NPC cells, but only slightly in an immortalized normal nasopharyngeal cell line. Taurine suppressed colony formation and induced apoptosis of NPC cell lines in a dose-dependent manner. Furthermore, taurine increased the active form of caspase-9/3 in a dose-dependent manner. Taurine down-regulated the anti-apoptotic protein Bcl-xL and up-regulated the pro-apoptotic protein Bax and GRP78, a major endoplasmic reticulum (ER) chaperone. These results suggest the involvement of mitochondrial and ER stress signaling in apoptosis. In addition, taurine increased the levels of PTEN (phosphatase and tensin homolog deleted on chromosome 10) and p53, and reduced phosphorylated Akt (protein kinase B). In conclusion, taurine may inhibit cell proliferation and induce apoptosis in NPC through PTEN activation with concomitant Akt inactivation.
鼻咽癌（NPC）是一种独特的头颈部恶性肿瘤，在中国南方的发病率较高。先前的研究已经证实，牛磺酸通过抑制细胞增殖和诱导细胞凋亡，对多种人类肿瘤具有抗癌作用。然而，其对 NPC 的抗癌作用的潜在分子机制尚不清楚。为了阐明这些抗癌机制，我们进行了细胞活力和集落形成测定。通过流式细胞术定量凋亡细胞。通过 Western blot 评估凋亡相关蛋白的表达水平。结果表明，牛磺酸显著抑制 NPC 细胞的增殖，但对永生化正常鼻咽细胞系的影响很小。牛磺酸以剂量依赖性方式抑制 NPC 细胞系的集落形成并诱导细胞凋亡。此外，牛磺酸以剂量依赖性方式增加活性形式的 caspase-9/3。牛磺酸下调抗凋亡蛋白 Bcl-xL，上调促凋亡蛋白 Bax 和内质网（ER）主要伴侣 GRP78。这些结果表明细胞凋亡涉及线粒体和 ER 应激信号。此外，牛磺酸增加了 PTEN（染色体 10 上缺失的磷酸酶和张力蛋白同源物）和 p53 的水平，并降低了磷酸化 Akt（蛋白激酶 B）的水平。总之，牛磺酸可能通过激活 PTEN 并同时失活 Akt 来抑制 NPC 中的细胞增殖并诱导细胞凋亡。
