Aims: Aloe-emodin (AE), a natural hydroxyanthraquinone compound, has been reported as a potential anticancer agent. We studied the antineoplastic properties of AE on highly metastatic B16-F10 melanoma murine cells.
Main methods: Cell proliferation was assessed by cell counting and viability was investigated using MTT and Trypan Bleu exclusion tests. As a growth marker, we determined intracellular polyamine levels by high performance liquid chromatography. Then, we evaluated transglutaminase 2 (TG2) activity, protoporphyrin IX accumulation and melanin content as differentiative markers. Tyrosinase activity was checked by DOPA-staining assay. The antimetastatic effect of AE was evaluated by means of a series of in vitro metastatic assays, including aggregation, wound healing migration, adhesion, 3D-invasion, circular invasion and the Boyden chamber invasion assays. Gelatin zymography was performed to evaluate metalloproteinase activities.
Key findings: Our results demonstrated inhibitory effects of AE on melanoma cell proliferation and invasion power, accompanied by the stimulation of cell differentiation parameters. Cell differentiation correlated with a remarkable increase of the activity of the transamidating form of TG2, with a significative enhancement of cell adhesion and aggregation. Impaired invasion was paralleled by the decrease of the secretion of matrix metalloproteinase-9.
Significance: The overall data confirm a remarkable antiproliferative, antimetastatic and differentiative capability of this anthraquinone. Results suggest that AE appears particularly promising for its potential application in the newborn differentiation therapy of cancer.
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