TY - JOUR
T1 - Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16-F10 melanoma cells
AU - Tabolacci, Claudio
AU - Lentini, Alessandro
AU - Mattioli, Palma
AU - Provenzano, Bruno
AU - Oliverio, Serafina
AU - Carlomosti, Fabrizio
AU - Beninati, Simone
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - Aloe-emodin
KW - Melanogenesis
KW - Melanoma
KW - Metastasis
KW - Transglutaminase
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U2 - 10.1016/j.lfs.2010.07.003
DO - 10.1016/j.lfs.2010.07.003
M3 - Article
C2 - 20624404
AN - SCOPUS:77955776103
VL - 87
SP - 316
EP - 324
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 9-10
ER -