Zeaxanthin Induces Apoptosis in Human Uveal Melanoma Cells through Bcl-2 Family Proteins and Intrinsic Apoptosis PathwayReportar como inadecuado




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Evidence-Based Complementary and Alternative MedicineVolume 2013 2013, Article ID 205082, 12 pages

Research Article

Department of Ophthalmology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun 130021, China

Department of Ophthalmology, The New York Eye and Ear Infirmary, New York Medical College, 310 E. 14th Street, New York, NY 10003, USA

Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA

Tissue Culture Center, The New York Eye and Ear Infirmary, New York Medical College, New York, NY 10003, USA

Department of Pathology, The New York Eye and Ear Infirmary, New York Medical College, 310 E. 14th Street, New York, NY 10003, USA

Received 26 July 2013; Accepted 3 September 2013

Academic Editor: Shun-Fa Yang

Copyright © 2013 Ming-Chao Bi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The cytotoxic effects of zeaxanthin on two human uveal melanoma cell lines SP6.5 and C918 and related signaling pathways were studied and compared to effects on normal ocular cells uveal melanocytes, retinal pigment epithelial cells, and scleral fibroblasts. MTT assay revealed that zeaxanthin reduced the cell viability of melanoma cells in a dose-dependent manner 10, 30, and 100 μM, with IC50 at 40.8 and 28.7 μM in SP6.5 and C918 cell lines, respectively. Zeaxanthin did not affect the viability of normal ocular cells even at the highest levels tested 300 μM, suggesting that zeaxanthin has a selectively cytotoxic effect on melanoma cells. Zeaxanthin induced apoptosis in melanoma cells as indicated by annexin V and ethidium III flow cytometry. Western blot analysis demonstrated that zeaxanthin decreased the expression of antiapoptotic proteins Bcl-2 and Bcl-xL and increased the expression of proapoptotic proteins Bak and Bax in zeaxanthin-treated melanoma cells. Zeaxanthin increased mitochondrial permeability as determined by JC-1 fluorescein study. Zeaxanthin also increased the level of cytosol cytochrome c and caspase-9 and -3 activities, but not caspase-8, as measured by ELISA assay or colorimetric assay. All of these findings indicate that the intrinsic mitochondrial pathway is involved in zeaxanthin-induced apoptosis in uveal melanoma cells.





Autor: Ming-Chao Bi, Richard Rosen, Ren-Yuan Zha, Steven A. McCormick, E. Song, and Dan-Ning Hu

Fuente: https://www.hindawi.com/



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