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Silymarin inhibits melanoma cell growth both in vitro and in vivo by targeting cell cycle regulators, angiogenic biomarkers and induction of apoptosis
Author(s) -
Vaid Mudit,
Singh Tripti,
Prasad Ram,
Katiyar Santosh K.
Publication year - 2015
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22208
Subject(s) - melanoma , biology , cancer research , apoptosis , cell cycle , cell growth , oncogene , cell cycle checkpoint , uvb induced apoptosis , programmed cell death , silybum marianum , cyclin b1 , caspase , cyclin dependent kinase 1 , biochemistry , genetics , botany
Cutaneous malignant melanoma is the leading cause of death from skin diseases and is often associated with activating mutations of the proto‐oncogene BRAF . To develop more effective strategies for the prevention or treatment of melanoma, we have examined the inhibitory effects of silymarin, a flavanoid from Silybum marianum , on melanoma cells. Using A375 ( BRAF ‐mutated) and Hs294t (non BRAF ‐mutated but highly metastatic) human melanoma cell lines, we found that in vitro treatment with silymarin resulted in a dose‐dependent: ( i ) reduction in cell viability; ( ii ) enhancement of either Go/G1 (A375) or G2‐M (Hs294t) phase cell cycle arrest with corresponding alterations in cyclins and cyclin‐dependent kinases; and ( iii ) induction of apoptosis. The silymarin‐induced apoptosis of human melanoma cells was associated with a reduction in the levels of anti‐apoptotic proteins (Bcl‐2 and Bcl‐xl), an increase in the levels of pro‐apoptotic protein (Bax), and activation of caspases. Further, oral administration of silymarin (500 mg/kg body weight/2× a week) significantly inhibited (60%, P < 0.01) the growth of BRAF ‐mutated A375 melanoma tumor xenografts, and this was associated with: ( i ) inhibition of cell proliferation; ( ii ) induction of apoptosis of tumor cells; ( iii ) alterations in cell cycle regulatory proteins; and ( iv ) reduced expression of tumor angiogenic biomarkers in tumor xenograft tissues. These results indicate that silymarin may have a chemotherapeutic effect on human melanoma cell growth and warrant its further evaluation. © 2014 Wiley Periodicals, Inc.