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Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells.

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Nicholas Oberlies, Associate Professor (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: Silymarin and, one of its constituents, silibinin exert strong efficacy against prostate cancer (PCA); however, anticancer efficacy and associated mechanisms of other components of silymarin, which is a mixture of flavonolignans, are largely unknown. Here we have assessed the anticancer efficacy of two pure compounds isosilybin B and isosilybin A, isolated from silymarin, in human prostate carcinoma LNCaP and 22Rv1 cells. Isosilybin B and isosilybin A treatment resulted in growth inhibition and cell death together with a strong G1 arrest and apoptosis in both the cell lines. In the studies examining changes in cell cycle and apoptosis regulators, isosilybin B and isosilybin A resulted in a decrease in the levels of both cyclins (D1, D3, E and A) and cyclin-dependent kinases (Cdk2, Cdk4 and cell division cycle 25A), but caused an increase in p21, p27 and p53 levels, except in 22Rv1 cells where isosilybin B caused a decrease in p21 protein level. Isosilybin B- and isosilybin A-induced apoptosis was accompanied with an increase in the cleavage of poly (ADP-ribose) polymerase, caspase-9 and caspase-3 and a decrease in survivin levels. Compared with LNCaP and 22Rv1 cells, the antiproliferative and cytotoxic potentials of isosilybin B and isosilybin A were of much lesser magnitude in non-neoplastic human prostate epithelial PWR-1E cells suggesting the transformation-selective effect of these compounds. Together, this study for the first time identified that isosilybin B and isosilybin A, two diastereoisomers isolated from silymarin, have anti-PCA activity that is mediated via cell cycle arrest and apoptosis induction. Abbreviations: PCA, prostate cancer; PI, propidium iodide; CDK, cyclin-dependent kinase; CDKI, cyclin-dependent kinase inhibitor; Cdc25A, cell division cycle 25A; PARP, poly (ADP-ribose) polymerase

Additional Information

Publication
Carcinogenesis 28, 1533-1542
Language: English
Date: 2007
Keywords
Silymarin, Prostate cancer, Isosilybin B, Isosilybin A