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.
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Authors | Gagan Deep, Nicholas H Oberlies, David J Kroll, Rajesh Agarwal |
Journal | Carcinogenesis
(Carcinogenesis)
Vol. 28
Issue 7
Pg. 1533-42
(Jul 2007)
ISSN: 0143-3334 [Print] England |
PMID | 17389612
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Anticarcinogenic Agents
- Antineoplastic Agents, Phytogenic
- BIRC5 protein, human
- Cell Cycle Proteins
- Cyclin-Dependent Kinase Inhibitor Proteins
- Inhibitor of Apoptosis Proteins
- Microtubule-Associated Proteins
- Neoplasm Proteins
- Silymarin
- Survivin
- Cyclin-Dependent Kinases
- Caspases
- isosilybin A
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Topics |
- Anticarcinogenic Agents
(pharmacology)
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
- Caspases
(metabolism)
- Cell Cycle
(drug effects)
- Cell Cycle Proteins
(metabolism)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cyclin-Dependent Kinase Inhibitor Proteins
(metabolism)
- Cyclin-Dependent Kinases
(metabolism)
- Enzyme Activation
- Humans
- Inhibitor of Apoptosis Proteins
- Male
- Microtubule-Associated Proteins
(metabolism)
- Neoplasm Proteins
(metabolism)
- Prostatic Neoplasms
- Silymarin
(analogs & derivatives, chemistry, isolation & purification, pharmacology)
- Stereoisomerism
- Survivin
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