Regulation of the extracellular matrix remodeling by lutein in dermal fibroblasts, melanoma cells, and ultraviolet radiation exposed fibroblasts

Abstract

With aging and cancer there is increased expression or activity of matrix metalloproteinases (MMPs) that degrade and remodel the structural extracellular matrix (ECM). In addition, exposure of skin to ultraviolet (UV) radiation (photoaging) leads to loss of cell viability, membrane damage, and deposition of excessive elastotic material. Lutein has antioxidant, anti-inflammatory, photoprotective, and anti-carcinogenic properties. The goal of this research was to investigate lutein's anti-aging and anti-carcinogenic effects via the regulation of the extracellular matrix remodeling. To this purpose, the effects of lutein on the expression of MMPs and their inhibitors (TIMPs, tissue inhibitors of metalloproteinases) in dermal fibroblasts (intrinsic aging) and melanoma cells were examined. Further, for lutein's photoprotective effects, the regulation of cell viability, membrane integrity, and elastin expression in the non-irradiated, and UVA or UVB radiation exposed fibroblasts were analyzed. Lutein significantly inhibited MMP-1 expression, transcriptionally, and MMP-2 protein levels in dermal fibroblasts, without altering TIMPs expression. It significantly inhibited MMP-1 expression in melanoma cells while stimulating TIMP-2. Lutein did not alter fibroblast or melanoma cell viability or membrane integrity. In ultraviolet radiation exposed fibroblasts, lutein improved cell viability, membrane integrity and inhibited elastin expression, though more significantly in the UVB exposed fibroblasts. In summary, the mechanism to lutein's anti-aging and anti-carcinogenic effects include the inhibition of MMP to TIMP ratio in dermal fibroblasts and melanoma cells, and the inhibition of cell loss, membrane damage and elastin expression in ultraviolet radiation exposed fibroblasts.

Beneficial Regulation of Elastase Activity and Expression of Tissue Inhibitors of Matrixmetalloproteinases, Fibrillin, Transforming Growth Factor-β, and Heat Shock Proteins by P. leucotomos in Nonirradiated or Ultraviolet-Radiated Epidermal Keratinocytes

“…The structural integrity of the ECM is compromised with the increase in the basal or induced levels of MMPs/elastase enzymes as well as their activity with aging or exposure to UV radiation. The ECM proteolytic enzymes (MMPs/elastases) are produced by epidermal keratinocytes, dermal fibroblasts, neutrophils and melanoma cells in the mediation of skin aging or cancer [3,[15][16][17][18]. P. leucotomos extract directly inhibits the activities of MMPs (MMP-1, 2, 3, 9) as well as the cellular expression of MMPs (MMP-1, 2) in nonirradiated or UV radiated dermal fibroblasts or epidermal keratinocytes [2,3].…”

“…Along with the increase in MMPs, there is decrease in TIMPs with aging or photoaging, which increases the cellular MMPs/TIMPs ratio and ECM damage [9][10][11]18]. P. leucotomos extract stimulates the expression of TIMPs in nonirradiated or UV radiated dermal fibroblasts [3].…”

“…A major regulator of the ECM proteins is TGF-, which stimulates the expression of TIMPs and fibrillin [10,18,21]. UV radiation counteracts the expression or effect of TGFin dermal fibroblasts, and keratinocytes [10,11].…”

Elastin Accumulation in Actinic Cheilitis with Different Degrees of Epithelial Dysplasia

“…According to Wondrak et al (2003), repetitive stimulation of the ECM proteins by solar radiation interferes with the integrity of the genome and contributes to photoaging and carcinogenesis of human skin. This excessive exposure to radiation results in the loss of cell viability, cell membrane damage and accumulation of elastotic material that replaces the normal collagen, resulting in a modified architectural pattern in sun-damaged skin known as solar elastosis (Philips et al, 2007). Therefore, the degradation of ECM macromolecules and elastosis increases the risk of developing cancers (Yano et al, 2005).…”

An Overview on the Role of Macular Xanthophylls in Ocular Diseases

“…Lutein and zeaxanthin, which are also called macular xanthophylls, show their effects by filtering high energy visible light, mostly with a peak of absorption at 446 nm and ultraviolet radiation lesser, inhibiting lipid peroxidation and reducing reactive species such as singlet oxygen and hydroxyl radical [46][47][48]. These carotenoids have several benefits on human health, including neuroprotective effects [49][50][51], anti-carcinogenic effects [52][53][54][55], anti-diabetic effects [56][57][58], cardioprotective effects [59][60][61], protective effects on skin damages and ocular diseases [62][63][64][65]. Particularly, several studies showed the role of lutein and zeaxanthin in eye diseases.…”