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

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.

Inactivated Sendai Virus Strain Tianjin Induces Apoptosis in Human Breast Cancer MDA-MB-231 Cells

“…The mitochondrial pathway is regulated by the Bcl-2 family proteins which includes the anti-apoptotic proteins (Bcl-2, etc. ), the proapoptotic proteins (Bax and Bak) (Bi et al, 2013). Accumulation of proapoptotic proteins on the mitochondrial outer membrane results in increased mitochondrial membrane permeability, causing the release of cyt c into the cytoplasm (Strasser et al, 2011).…”

Thymoquinone, a bioactive component of Nigella sativa Linn seeds or traditional spice, attenuates acute hepatic failure and blocks apoptosis via the MAPK signaling pathway in mice

“…4 In addition, it is reported that D-GalN/LPS induced MAPK activation in mice. 7 Thymoquinone (TQ), a bioactive natural product obtained from the black cumin seeds of Nigella sativa Linn, is a widely used spice or herb throughout India and the Middle East. 6 Apoptosis can be induced through extrinsic pathway followed by caspase-8 activation and via the mitochondrial pathway by triggering the Bcl-2 family.…”

Role of Zucchini and Its Distinctive Components in the Modulation of Degenerative Processes: Genotoxicity, Antigenotoxicity, Cytotoxicity and Apoptotic Effects

“…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; in addition, zeaxanthin (30 μM) induced apoptosis in melanoma cells [28].…”

“…Lutein and zeaxanthin, naturally occurring carotenoids, have shown to reduce the risk of cataracts and age-related macular degeneration [27]. Zeaxanthin is related with the reduction of melanoma cells viability [28]. Lutein caused significant DNA damage in human retinal pigment epithelial cells [29].…”