Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human
breast cancer cells MDA-MB 468: induction of G1 arrest through an increase in
Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent
kinases and associated cyclins.
Zi X, Feyes DK, Agarwal R.
Department of Dermatology, Case Western Reserve University, Cleveland, Ohio
There is an increasing interest in identifying potent cancer preventive and
therapeutic agents against breast cancer. Silymarin, a flavonoid antioxidant
isolated from milk thistle, exerts exceptionally high to complete
anticarcinogenic effects in tumorigenesis models of epithelial origin.
this study, we investigated the anticarcinogenic effect of silymarin and
associated molecular mechanisms, using human breast carcinoma cells MDA-MB
Silymarin treatment resulted in a significantly high to complete
inhibition of both anchorage-dependent and anchorage-independent cell growth
in a dose- and time-dependent manner. The inhibitory effects of silymarin on
cell growth and proliferation were associated with a G1 arrest in cell cycle
progression concomitant with an induction of up to 19-fold in the protein
expression of cyclin-dependent kinase (CDK) inhibitor Cip1/p21.
silymarin treatment of cells, an incremental binding of Cip1/p21 with CDK2
and CDK6 paralleled a significant decrease in CDK2-, CDK6-, cyclin D1-, and
cyclin E-associated kinase activity with no change in CDK2 and CDK6
expression but a decrease in G1 cyclins D1 and E. Taken together, these
results suggest that silymarin may exert a strong anticarcinogenic effect
against breast cancer and that this effect possibly involves an induction of
Cip1/p21 by silymarin, which inhibits the threshold kinase activities of CDKs
and associated cyclins, leading to a G1 arrest in cell cycle progression.
PMID: 9563902 [PubMed - indexed for MEDLINE]
Clin Cancer Res 1998 Apr;4(4):1055-64
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