Nonlethal Levels of Zeaxanthin Inhibit Cell Migration, Invasion, and Secretion of MMP-2 via NF-<i>κ</i>B Pathway in Cultured Human Uveal Melanoma Cells

Bi, Mingchao; Hose, Nicole; Xu, Cailian; Zhang, Chen; Sassoon, Jodi; Song, E

doi:10.1155/2016/8734309

Cited by 16 publications

(10 citation statements)

References 33 publications

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“…The zeaxanthin-rich extracts from Goji Erma (1) and Biglifeberry (2) inhibited at some extent the fibroblast proliferation in vitro, these results being in accordance with previous studies [ 7 ]. Zeaxanthin effect was dissimilar to those of glycoconjugates from Goji, which promoted the survival of human fibroblasts [ 20 ].…”

Section: Discussionsupporting

confidence: 91%

“…The upregulation of the NF-kβ indicates cancer progression, and many natural products were identified as blockers of this signaling pathway [ 39 ]. In the case of L. barbarum extracts 1 and 2 , no inhibition of p65 intracytoplasmic translocation was observed in A375 cells ( Figure 5 ), while in uveal melanoma the inhibition of NF-kB pathway was reported [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…Instead, the melanoma cells growth and migration are hindered by zeaxanthin [ 6 ]. Previous experiments [ 7 ] demonstrated that the activity of zeaxanthin at 1 μM was not significantly different from the controls, but at higher concentrations it manifested a cytotoxic effect on cultured human uveal melanoma cells (3–10 μM) and respectively on BJ cells proliferation (100–300 μM). Zeaxanthin at high dosage of 10.0 μM lowered NF-kβ levels due to the inhibition of NF- kβ pathway in uveal melanoma cells [ 7 ].…”

Section: Introductionmentioning

confidence: 95%

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Zeaxanthin-Rich Extract from Superfood Lycium barbarum Selectively Modulates the Cellular Adhesion and MAPK Signaling in Melanoma versus Normal Skin Cells In Vitro

et al. 2021

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The concern for implementing bioactive nutraceuticals in antioxidant-related therapies is of great importance for skin homeostasis in benign or malignant diseases. In order to elucidate some novel insights of Lycium barbarum (Goji berry) activity on skin cells, the present study focused on its active compound zeaxanthin. By targeting the stemness markers CD44 and CD105, with deep implications in skin oxidative stress mechanisms, we revealed, for the first time, selectivity in zeaxanthin activity. When applied in vitro on BJ human fibroblast cell line versus the A375 malignant melanoma cells, despite the moderate cytotoxicity, the zeaxanthin-rich extracts 1 and 2 were able to downregulate significantly the CD44 and CD105 membrane expression and extracellular secretion in A375, and to upregulate them in BJ cells. At mechanistic level, the present study is the first to demonstrate that the zeaxanthin-rich Goji extracts are able to influence selectively the mitogen-activated protein kinases (MAPK): ERK, JNK and p38 in normal BJ versus tumor-derived A375 skin cells. These results point out towards the applications of zeaxanthin from L. barbarum as a cytoprotective agent in normal skin and raises questions about its use as an antitumor prodrug alone or in combination with standard therapy.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Zeaxanthin-Rich Extract from Superfood Lycium barbarum Selectively Modulates the Cellular Adhesion and MAPK Signaling in Melanoma versus Normal Skin Cells In Vitro

et al. 2021

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“…Among the 23 MMPs identified in humans [ 19 ], MMP-2 is widely expressed in tissues and cells [ 20 ]. Recently, the levels of MMP-2 secretion were directly used to evaluate the migration of various types of cells [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

All-Trans Retinoic Acid Enhances Matrix Metalloproteinase 2 Expression and Secretion in Human Myeloid Leukemia THP-1 Cells

Hoang

Kim

2018

BioMed Research International

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All-trans retinoic acid (ATRA) is an effective drug for the induction therapy of acute promyelocytic leukemia. However, the treatment is associated with adverse events such as retinoic acid syndrome (RAS) in some patients, whose histologic characteristics included organ infiltration by leukemic cells. Matrix metalloproteinase 2 (MMP-2) is often upregulated in tumor cells and plays a role in tumor cell migration and invasion by degrading the extracellular matrix. In this study, we examined the possible modulatory effects of ATRA on MMP-2 expression and secretion in human myeloid leukemia cell line THP-1. The cells were treated with various concentrations of ATRA, and MMP-2 expression and secretion were examined. MMP-2 expression and secretion started to increase with ATRA concentration as low as 0.1 nM and gradually increased thereafter. Agonists of retinoic acid receptor (RAR) or retinoid X receptor (RXR) alone could enhance MMP-2 secretion, and RAR or RXR antagonists alone could reverse ATRA-induced MMP-2 secretion. ATRA increased intracellular calcium ion levels, and a calcium-channel blocker inhibited ATRA-induced MMP-2 secretion. Dexamethasone suppressed ATRA-induced MMP-2 secretion. Our results suggest that ATRA enhances MMP-2 expression and secretion in human myeloid leukemia THP-1 cells in a calcium ion dependent manner through RAR/RXR signaling pathways, and this enhanced expression and secretion may be associated with the possible mechanisms of RAS.

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“…Further experimental evidence indicated that MMPs mediate UM cell invasiveness in vitro [112] and in xenograft models. Indeed, inhibition of MMP2 expression and/or activity by epigallocatechin gallate [113] or zeaxanthin [114] inhibited UM cell invasiveness, supporting a potential role of MMP2 inhibitors in the prevention of UM metastases.…”

Section: Targeting Hyper-expressed Molecules Involved In Progressionmentioning

confidence: 99%

Targeted Therapy of Uveal Melanoma: Recent Failures and New Perspectives

Croce

Ferrini

Pfeffer

et al. 2019

Cancers

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Among Uveal Melanoma (UM) driver mutations, those involving GNAQ or GNA11 genes are the most frequent, while a minor fraction of tumors bears mutations in the PLCB4 or CYSLTR2 genes. Direct inhibition of constitutively active oncoproteins deriving from these mutations is still in its infancy in UM, whereas BRAFV600E-targeted therapy has obtained relevant results in cutaneous melanoma. However, UM driver mutations converge on common downstream signaling pathways such as PKC/MAPK, PI3K/AKT, and YAP/TAZ, which are presently considered as actionable targets. In addition, BAP1 loss, which characterizes UM metastatic progression, affects chromatin structure via histone H2A deubiquitylation that may be counteracted by histone deacetylase inhibitors. Encouraging results of preclinical studies targeting signaling molecules such as MAPK and PKC were unfortunately not confirmed in early clinical studies. Indeed, a general survey of all clinical trials applying new targeted and immune therapy to UM displayed disappointing results. This paper summarizes the most recent studies of UM-targeted therapies, analyzing the possible origins of failures. We also focus on hyperexpressed molecules involved in UM aggressiveness as potential new targets for therapy.

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Nonlethal Levels of Zeaxanthin Inhibit Cell Migration, Invasion, and Secretion of MMP-2 via NF-κB Pathway in Cultured Human Uveal Melanoma Cells

Cited by 16 publications

References 33 publications

Zeaxanthin-Rich Extract from Superfood Lycium barbarum Selectively Modulates the Cellular Adhesion and MAPK Signaling in Melanoma versus Normal Skin Cells In Vitro

Zeaxanthin-Rich Extract from Superfood Lycium barbarum Selectively Modulates the Cellular Adhesion and MAPK Signaling in Melanoma versus Normal Skin Cells In Vitro

All-Trans Retinoic Acid Enhances Matrix Metalloproteinase 2 Expression and Secretion in Human Myeloid Leukemia THP-1 Cells

Targeted Therapy of Uveal Melanoma: Recent Failures and New Perspectives

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