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silymarin targets β-catenin signaling in blocking migrationinvasion of human melanoma cells水飞蓟素目标β-catenin信号阻塞migrationinvasion人类黑色素瘤细胞
Silymarin Targets b-Catenin Signaling in Blocking
Migration/Invasion of Human Melanoma Cells
1 1 1 1,2,3
Mudit Vaid , Ram Prasad , Qian Sun , Santosh K. Katiyar *
1 Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 Comprehensive Cancer Center, University of
Alabama at Birmingham, Birmingham, Alabama, United States of America, 3 Birmingham VA Medical Center, Birmingham, Alabama, United States of America
Abstract
Metastatic melanoma is a leading cause of death from skin diseases, and is often associated with activation of Wnt/b-catenin
signaling pathway. We have examined the inhibitory effect of silymarin, a plant flavanoid from Silybum marianum, on cell
migration of metastasis-specific human melanoma cell lines (A375 and Hs294t) and assessed whether Wnt/b-catenin
signaling is the target of silymarin. Using an in vitro invasion assay, we found that treatment of human melanoma cell lines
with silymarin resulted in concentration-dependent inhibition of cell migration, which was associated with accumulation of
cytosolic b-catenin, while reducing the nuclear accumulation of b-catenin (i.e., b-catenin inactivation) and reducing the
levels of matrix metalloproteinase (MMP) -2 and MMP-9 which are the down-stream targets of b-catenin. Silymarin
enhanced: (i) the levels of casein kinase 1a, glycogen synthase kinase-3b and phosphorylated-b-catenin on critical residues
Ser45, Ser33/37 and Thr41, and (ii) the binding of b-transducin repeat-containing proteins (b-TrCP) with phospho forms of b-
catenin in melanoma cells. These events play important roles in degradation or inactivation of b-catenin. To verify whether
b-catenin is a po
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