Class III-specific HDAC inhibitor Tenovin-6 induces apoptosis, suppresses migration and eliminates cancer stem cells in uveal melanoma.
Class III-specific HDAC inhibitor Tenovin-6 induces apoptosis, suppresses migration and eliminates cancer stem cells in uveal melanoma.
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III 类特异性 HDAC 抑制剂 Tenovin-6 诱导细胞凋亡、抑制迁移并消除葡萄膜黑色素瘤中的癌症干细胞
DOI：
10.1038/srep22622
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发表时间：
2016-03-04
影响因子：
4.6
通讯作者：
Pan J
中科院分区：
文献类型：
--
作者：
Dai W;Zhou J;Jin B;Pan J
葡萄膜黑色素瘤（UM）是成人最常见的眼内恶性肿瘤。尽管手术、放疗和化疗治疗有所改善，但UM的总体生存率和预后仍然很差。在本研究中，我们假设Sirtuin 1和2（SIRT 1/2）（III类组蛋白脱乙酰酶（HDAC））在控制UM大量肿瘤细胞和癌症干细胞（CSC）的命运方面至关重要。我们在四个UM细胞系（92.1，Mel 270，Omm 1和Omm 2.3）中证实了这一假设。我们的研究结果表明，Tenovin-6抑制SIRT 1/2通过激活肿瘤抑制基因如p53的表达和升高活性氧（ROS）诱导UM细胞凋亡。Tenovin-6抑制UM细胞的生长。Tenovin-6和长春碱在诱导UM细胞系92.1和Mel 270凋亡方面具有协同作用。此外，Tenovin-6消除了92.1和Mel 270细胞中的癌症干细胞。总之，我们的研究结果表明，Tenovin-6可能是一种有前途的药物，以杀死UM散装肿瘤细胞和CSC。
Uveal melanoma (UM) is the most common intraocular malignancy in adults. Despite improvements in surgical, radiation and chemotherapy treatments, the overall survival of UM and prognosis remain poor. In the present study, we hypothesized that Sirtuin 1 and 2 (SIRT1/2), class III histone deacetylases (HDACs), were critical in controlling the destiny of bulk tumor cells and cancer stem cells (CSCs) of UM. We testified this hypothesis in four lines of UM cells (92.1, Mel 270, Omm 1 and Omm 2.3). Our results showed that inhibition of SIRT1/2 by Tenovin-6 induced apoptosis in UM cells by activating the expression of tumor suppressor genes such as p53 and elevating reactive oxygen species (ROS). Tenovin-6 inhibited the growth of UM cells. Tenovin-6 and vinblastine was synergistic in inducing apoptosis of UM cell line 92.1 and Mel 270. Furthermore, Tenovin-6 eliminated cancer stem cells in 92.1 and Mel 270 cells. In conclusion, our findings suggest that Tenovin-6 may be a promising agent to kill UM bulk tumor cells and CSCs.