Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells.
Extracts from the seeds of milk thistle, Silybum marianum, are known commonly as silibinin and silymarin and possess anticancer actions on human prostate carcinoma in vitro and in vivo. Seven distinct flavonolignan compounds and a flavonoid have been isolated from commercial silymarin extracts. Most notably, two pairs of diastereomers, silybin A and silybin B and isosilybin A and isosilybin B, are among these compounds. In contrast, silibinin is composed only of a 1:1 mixture of silybin A and silybin B. With these isomers now isolated in quantities sufficient for biological studies, each pure compound was assessed for antiproliferative activities against LNCaP, DU145, and PC3 human prostate carcinoma cell lines. Isosilybin B was the most consistently potent suppressor of cell growth relative to either the other pure constituents or the commercial extracts. Isosilybin A and isosilybin B were also the most effective suppressors of prostate-specific antigen secretion by androgen-dependent LNCaP cells. Silymarin and silibinin were shown for the first time to suppress the activity of the DNA topoisomerase IIalpha gene promoter in DU145 cells and, among the pure compounds, isosilybin B was again the most effective. These findings are significant in that isosilybin B composes no more than 5% of silymarin and is absent from silibinin. Whereas several other more abundant flavonolignans do ultimately influence the same end points at higher exposure concentrations, these findings are suggestive that extracts enriched for isosilybin B, or isosilybin B alone, might possess improved potency in prostate cancer prevention and treatment.
Davis-Searles
Paula R
PR
Natural Products Laboratory, Research Triangle Institute, Research Triangle Park, North Carolina 27709-2194, USA.
Nakanishi
Yuka
Y
Kim
Nam-Cheol
NC
Graf
Tyler N
TN
Oberlies
Nicholas H
NH
Wani
Mansukh C
MC
Wall
Monroe E
ME
Agarwal
Rajesh
R
Kroll
David J
DJ
D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D044947:Flavonolignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D020944:Silybum marianum / Q000737:chemistry*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D059005:Topoisomerase II Inhibitors
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D044947:Flavonolignans; D010936:Plant Extracts; D059005:Topoisomerase II Inhibitors; D017430:Prostate-Specific Antigen; D004250:DNA Topoisomerases, Type II