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Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells.
Int J Cancer 2008; 123(1):41-50IJ

Abstract

Prostate cancer (PCa) is the leading cause of cancer-related deaths in men; urgent measures are warranted to lower this deadly malignancy. Silymarin is a known cancer chemopreventive agent, but the relative anticancer efficacy of its constituents is still unknown. Here, we compared the efficacy of 7 pure flavonolignan compounds isolated from silymarin, namely silybin A, silybin B, isosilybin A, isosilybin B, silydianin, isosilydianin, silychristin and isosilychristin, in advanced human PCa PC3 cells. Silybin A, silybin B, isosilybin A, isosilybin B, silibinin and silymarin strongly inhibited the colony formation by PC3 cells (p < 0.001), while silydianin, silychristin and isosilychristin had marginal effect (p < 0.05). Using cell growth and death assays, we identified isosilybin B as the most effective isomer. FACS analysis for cell cycle also showed that silybin A, silybin B, isosilybin A, isosilybin B, silibinin and silymarin treatment resulted in strong cell cycle arrest in PC3 cells after 72 hr of treatment, while the effect of silydianin, silychristin and isosilychristin was marginal (if any). Western blot analysis also showed the differential effect of these compounds on the levels of cell cycle regulators-cyclins (D, E, A and B), CDKs (Cdk2, 4 and Cdc2), CDKIs (p21 and p27) and other cell cycle regulators (Skp2, Cdc25A, B, C and Chk2). This study provided further evidence for differential anticancer potential among each silymarin constituent, which would have potential implications in devising better formulations of silymarin against prostate and other cancers.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Denver, CO 80262, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18435416

Citation

Deep, Gagan, et al. "Identifying the Differential Effects of Silymarin Constituents On Cell Growth and Cell Cycle Regulatory Molecules in Human Prostate Cancer Cells." International Journal of Cancer, vol. 123, no. 1, 2008, pp. 41-50.
Deep G, Oberlies NH, Kroll DJ, et al. Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells. Int J Cancer. 2008;123(1):41-50.
Deep, G., Oberlies, N. H., Kroll, D. J., & Agarwal, R. (2008). Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells. International Journal of Cancer, 123(1), pp. 41-50. doi:10.1002/ijc.23485.
Deep G, et al. Identifying the Differential Effects of Silymarin Constituents On Cell Growth and Cell Cycle Regulatory Molecules in Human Prostate Cancer Cells. Int J Cancer. 2008 Jul 1;123(1):41-50. PubMed PMID: 18435416.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells. AU - Deep,Gagan, AU - Oberlies,Nicholas H, AU - Kroll,David J, AU - Agarwal,Rajesh, PY - 2008/4/26/pubmed PY - 2008/6/3/medline PY - 2008/4/26/entrez SP - 41 EP - 50 JF - International journal of cancer JO - Int. J. Cancer VL - 123 IS - 1 N2 - Prostate cancer (PCa) is the leading cause of cancer-related deaths in men; urgent measures are warranted to lower this deadly malignancy. Silymarin is a known cancer chemopreventive agent, but the relative anticancer efficacy of its constituents is still unknown. Here, we compared the efficacy of 7 pure flavonolignan compounds isolated from silymarin, namely silybin A, silybin B, isosilybin A, isosilybin B, silydianin, isosilydianin, silychristin and isosilychristin, in advanced human PCa PC3 cells. Silybin A, silybin B, isosilybin A, isosilybin B, silibinin and silymarin strongly inhibited the colony formation by PC3 cells (p < 0.001), while silydianin, silychristin and isosilychristin had marginal effect (p < 0.05). Using cell growth and death assays, we identified isosilybin B as the most effective isomer. FACS analysis for cell cycle also showed that silybin A, silybin B, isosilybin A, isosilybin B, silibinin and silymarin treatment resulted in strong cell cycle arrest in PC3 cells after 72 hr of treatment, while the effect of silydianin, silychristin and isosilychristin was marginal (if any). Western blot analysis also showed the differential effect of these compounds on the levels of cell cycle regulators-cyclins (D, E, A and B), CDKs (Cdk2, 4 and Cdc2), CDKIs (p21 and p27) and other cell cycle regulators (Skp2, Cdc25A, B, C and Chk2). This study provided further evidence for differential anticancer potential among each silymarin constituent, which would have potential implications in devising better formulations of silymarin against prostate and other cancers. SN - 1097-0215 UR - https://www.unboundmedicine.com/medline/citation/18435416/Identifying_the_differential_effects_of_silymarin_constituents_on_cell_growth_and_cell_cycle_regulatory_molecules_in_human_prostate_cancer_cells_ L2 - https://doi.org/10.1002/ijc.23485 DB - PRIME DP - Unbound Medicine ER -