Toxicogenomics of A375 human malignant melanoma cells treated with arbutin

Abstract

Although arbutin is a natural product and widely used as an ingredient in skin care products, its effect on the gene expression level of human skin with malignant melanoma cells is rarely reported. We aim to investigate the genotoxic effect of arbutin on the differential gene expression profiling in A375 human malignant melanoma cells through its effect on tumorigenesis and related side-effect. The DNA microarray analysis provided the differential gene expression pattern of arbutin-treated A375 cells with the significant changes of 324 differentially expressed genes, containing 88 up-regulated genes and 236 down-regulated genes. The gene ontology of differentially expressed genes was classified as belonging to cellular component, molecular function and biological process. In addition, four down-regulated genes of AKT1, CLECSF7, FGFR3, and LRP6 served as candidate genes and correlated to suppress the biological processes in the cell cycle of cancer progression and in the downstream signaling pathways of malignancy of melanocytic tumorigenesis.

The Role of Phenolic Compounds in the Fight against Cancer – A Review

“…This same compound was found to potentiate the effect of paclitaxel, an anticancer commercial drug that inhibits cell mitosis [115]. Arbutin also displayed a remarkable effect against melanoma cell lines by down regulating cancer genes [116]. Szliszka et al [117] tested 2 chalcones (chalcone and 2',6'dihydroxy-4'-methoxychalcone) and 3 dihydrochalcones (2',6'-dihydroxy-4'4-dimethoxydihydrochalcone, 2',6'-dihydroxy-4'-methoxydihydrochalcone, and phloretin) against human prostate cancer cells and discovered that all the compounds induced TRAIL mediated apoptosis against the cell lines.…”

Anti-inflammatory effects of arbutin in lipopolysaccharide-stimulated BV2 microglial cells

“…In erythrocytes, arbutin shows long-lasting radical scavenging properties and also protects a membrane lipid from oxidative stress in human skin fibroblasts [8][9][10]. In cultured human melanoma cells (HMV-II and A375), mouse melanoma cells (B16), and a three-dimensional cultured human skin model, arbutin at concentrations below 300 lg/ ml decreased both tyrosinase activity and melanin content to 40 % of that in the control, thus blocking melanogenesis [11][12][13][14]. Recently, arbutin was effective in post-inflammatory hyperpigmentation (PIH), which is a reactive hypermelanosis and sequela of various inflammatory skin conditions [15], suggesting that arbutin can regulate not only radical-mediated stress, but also the inflammatory response.…”

Molecular Profiling of A375 Human Malignant Melanoma Cells Treated with Kojic Acid and Arbutin

“…Further functional studies of these proteins may lead to better understanding of the pathogenic mechanisms and cellular response to kojic acid treatment. According to our investigation of the toxicogenomic effects of arbutin on the gene expression profile of A375 melanoma cells using microarray 26 , there was no growth inhibition or morphological change of A375 melanoma cells after 72 h in the presence of 8 μg/ml arbutin, which is a mild arbutin concentration and safe for human skin. The gene expression data showed some tumor suppressor genes as biomarkers in A375 melanoma cells.…”

“…A375 melanoma cell growth was directly inhibited by increasing arbutin concentrations 26 . After 72 h, the highest concentration of arbutin (1000 μg/ml) inhibited A375 cell growth up to 40%, while the lower concentrations of 0.32, 1.6, 8 and 40 μg/ml arbutin inhibited cell growth by less than 20% (Fig.…”

“…The differences in Cy3 and Cy5 signal intensities with a p-value of less than 0.01 (p<0.01) were considered to be significantly different 26 . Table 4.…”