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

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 re...

Full description

Saved in:
Bibliographic Details
Published in:Evidence-based complementary and alternative medicine 2013-01, Vol.2013 (2013), p.1-12
Main Authors: Zha, Ren-Yuan, Bi, Ming-Chao, Hu, Dan-Ning, Song, E., McCormick, Steven A., Rosen, Richard
Format: Article
Language:English
Subjects:
Annexin V
Apoptosis
Assaying
BAX protein
Bcl-2 protein
Bcl-x protein
Cancer
Carotenoids
Caspase
Caspase-8
Caspase-9
Cell lines
Colorimetry
Cytochrome
Cytochrome c
Cytosol
Cytotoxicity
Enzyme-linked immunosorbent assay
Fibroblasts
Flow cytometry
Fluorescein
Gangrene
Gene expression
Macular degeneration
Melanocytes
Melanoma
Metastasis
Mitochondria
Permeability
Proteins
Retina
Retinal pigment epithelium
Zeaxanthin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1741-427X
1741-4288
DOI:10.1155/2013/205082