Effects of Humulus lupulus extract or its Components on Viability, Lipid Peroxidation, and expression of Vascular Endothelial Growth Factor in Melanoma Cells and Fibroblasts

Abstract

Cancer and aging are associated with altered cell viability and angiogenesis, which is mediated by vascular endothelial growth factor (VEGF). These alterations have been associated with cellular oxidative stress. Humuluslupulus (HOP) extract, and its components, which include alpha-acid, beta-acid, xanthoflavonoids, xanthohumunol, and isoxanthohumunol, exhibit antioxidant activity. This research examined the effects of HOP extract or its components on direct antioxidant activity, and on cell viability, lipid peroxidation, and expression of VEGF in melanoma cells, and dermal fibroblasts. The HOP extract, and its components exhibited direct antioxidant activity. In melanoma cells, HOP extract, and its components significantly inhibited cell viability and stimulated extracellular lipid hydroperoxides at all examined concentrations; and with few exceptions did not significantly alter intracellular lipid peroxidation or the expression of VEGF. In dermal fibroblasts, HOP extract and its components significantly inhibited cell viability and intracellular lipid peroxidation, and stimulated the expression at VEGF at the highest examined concentration; and with few exceptions did not significantly alter extracellular lipid peroxidation. It is inferred that HOP extract, and its components differentially and beneficially regulate the cellular biochemistry of melanoma cells, and fibroblasts for the management of cancer, and aging.

The Beneficial Regulation of Extracellular Matrix and Heat Shock Proteins, and the Inhibition of Cellular Oxidative Stress Effects and Inflammatory Cytokines by 1α, 25 dihydroxyvitaminD3 in Non-Irradiated and Ultraviolet Radiated Dermal Fibroblasts

“…The direct antioxidant activity of vitamin D was determined by an ABTS ® (2, 2 -azino-di-[3-ethylbenzthiazoline sulphonate]) assay, which is based on the inhibition of the oxidation of ABTS ® to an ABTS ® radical by metmyoglobin (Cayman Chemical Antioxidant Assay kit) [2,3]. Vitamin D at 0, 0.02, 0.2, or 2 µM was incubated with ABTS and metmyoglobin, and the inhibition of ABTS oxidation was measured spectrophotometrically at 405 nm.…”

“…The expression of the type I collagen, elastin, HSP-47, IL-1β, IL-8, and HSP-70 proteins was measured by indirect ELISA (Kirkguaard and Perry Laboratories, Inc, Gaithersburg, MD, USA) [1][2][3][9][10][11][12][13][14][15][16]. Aliquots of 9100 ul of the samples were placed in a 96 well plate for 24 h at 4 • C, blocked with bovine serum albumin for 30 min at room temperature and incubated with respective primary antibodies (Millipore, Burlington, MA, USA; Elastin products Co, Owensville, Missouri; StressGen, Farmingdale, NY; Sigma, Ronkonkoma, NY, USA) for 1 h at room temperature.…”

“…The structural integrity of the extracellular matrix (ECM) is essential to anti-aging [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. The structural ECM is composed largely of collagen and elastin fibers, which are synthesized by the dermal fibroblasts [9][10][11][12][13][14][15][16].…”

“…The ROS directly damage DNA to generate 8-oxo-7, 8-dihydro-2 -deoxyguanosine (8-oxo-dG) and pyrimidine dimmers, proteins to generate carbonyl amino acid derivatives, and lipids to generate lipid peroxides and lipid inflammatory mediators [4,5,[24][25][26][27]. Phenolic compounds have anti-oxidative and anti-inflammatory properties, and thereby anti-aging properties, because of their structure and the number and location of their hydroxyl groups [1][2][3][4][5][31][32][33].The structure of 1α, 25dihydroxyvitamin D3 (vitamin D) and its endocrine role in cellular homeostasis as well as its photoprotective and anti-inflammatory role makes it essential to skin health [34][35][36][37][38][39][40][41][42][43][44][45]. Vitamin D, or its analog, stimulates the expression of collagen and counteracts the glucocorticoid mediated inhibition of collagen synthesis in dermal fibroblasts [35,36].…”

“…The ROS directly damage DNA to generate 8-oxo-7, 8-dihydro-2 -deoxyguanosine (8-oxo-dG) and pyrimidine dimmers, proteins to generate carbonyl amino acid derivatives, and lipids to generate lipid peroxides and lipid inflammatory mediators [4,5,[24][25][26][27]. Phenolic compounds have anti-oxidative and anti-inflammatory properties, and thereby anti-aging properties, because of their structure and the number and location of their hydroxyl groups [1][2][3][4][5][31][32][33].…”