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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.
Carcinogenesis 2007; 28(7):1533-42C

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 G(1) 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.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17389612

Citation

Deep, Gagan, et al. "Isosilybin B and Isosilybin a Inhibit Growth, Induce G1 Arrest and Cause Apoptosis in Human Prostate Cancer LNCaP and 22Rv1 Cells." Carcinogenesis, vol. 28, no. 7, 2007, pp. 1533-42.
Deep G, Oberlies NH, Kroll DJ, et al. Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells. Carcinogenesis. 2007;28(7):1533-42.
Deep, G., Oberlies, N. H., Kroll, D. J., & Agarwal, R. (2007). Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells. Carcinogenesis, 28(7), pp. 1533-42.
Deep G, et al. Isosilybin B and Isosilybin a Inhibit Growth, Induce G1 Arrest and Cause Apoptosis in Human Prostate Cancer LNCaP and 22Rv1 Cells. Carcinogenesis. 2007;28(7):1533-42. PubMed PMID: 17389612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells. AU - Deep,Gagan, AU - Oberlies,Nicholas H, AU - Kroll,David J, AU - Agarwal,Rajesh, Y1 - 2007/03/26/ PY - 2007/3/29/pubmed PY - 2007/10/5/medline PY - 2007/3/29/entrez SP - 1533 EP - 42 JF - Carcinogenesis JO - Carcinogenesis VL - 28 IS - 7 N2 - 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 G(1) 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. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/17389612/Isosilybin_B_and_isosilybin_A_inhibit_growth_induce_G1_arrest_and_cause_apoptosis_in_human_prostate_cancer_LNCaP_and_22Rv1_cells_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgm069 DB - PRIME DP - Unbound Medicine ER -