In vitro and in vivo anti-uveal melanoma activity of JSL-1, a novel HDAC inhibitor. (1st August 2017)

• Record Type: Journal Article
• Authors: Wang, Yun; Liu, Maoxing; Jin, Yanli; Jiang, Sheng; Pan, Jingxuan
• Is Part Of: Cancer letters. Volume 400(2017)
• Page Start: 47
• Page End: 60
• Publication Date: 2017-08-01
• Subjects: Uveal melanoma -- Epigenetics -- HDAC inhibitor -- Migration and invasion -- β-catenin -- Cancer stem-like cells; UM uveal melanoma -- HDAC histone deacetylase -- HDACi HDAC inhibitor -- HAT histone acetyltransferase -- CSCs cancer stem-like cells -- ALDH aldehyde dehydrogenase -- PI propidium iodide -- AIF apoptosis-inducing factor -- MMP-2 matrix metalloproteinase 2 -- MAPK mitogen-activated protein kinase -- ERK1/2 extracellular regulating kinase 1/2 -- PEI polyethylenimine; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.04.028
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Uveal melanoma (UM) is the most common intraocular malignant neoplasm in adults. Despite the availability of enucleation, radiation and chemotherapy, the prognosis of patients with metastasis remains poor. Therefore, novel effective therapies for patients with metastatic UM are urgently needed. In the present study, we demonstrated that JSL-1, a novel HDAC inhibitor, effectively inhibited the proliferation. JSL-1 induced apoptosis with increased expression of proapoptotic BH3-only protein BIM in UM cells. JSL-1 suppressed migration and invasion of UM cells with MMP-2 decreased. Furthermore, JSL-1 blocked the canonical Wnt/β-catenin pathway, impaired self-renewal capacity and decreased percentage of ALDH + cells, thereby reflecting elimination of UM cancer stem-like cells (CSCs) which are believed seeds of metastasis. Importantly, JSL-1 potently inhibited the growth of uveal melanoma xenograft in NOD-SCID mice. These results suggested that JSL-1 may be a promising therapeutic agent for UM. Highlights: HDAC inhibitor JSL-1 against UM activity. BIM is identified as a leading gene related to apoptosis of UM cells. Targeting HDAC provides an approach for treating recalcitrant UM. HDAC inhibitor blocks Wnt/β-catenin signaling pathway.