Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells.
(1/13)
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. (+info)
New insight into the biosynthesis of flavanolignans in the white-flowered variant of Silybum marianum.
(2/13)
It has been demonstrated that besides the known flavanolignan constituents of the white-flowered variant of Silybum marianum, (-)-silandrin A (3a) and (-)-isosilandrin A (4a); their trans-benzodioxane diastereomers, (-)-silandrin B (3b) and (-)-isosilandrin B (4b), are also produced by the plant. Moreover, the isolation of their cis-benzodioxane diastereomers, (-)-isocisilandrin (5) and cisilandrin (6), confirm that the previously proposed biosynthetic pathway involving a nonselective O-beta coupling is correct. (+info)
Hepatic metabolism and biliary excretion of silymarin flavonolignans in isolated perfused rat livers: role of multidrug resistance-associated protein 2 (Abcc2).
(3/13)
Large-scale isolation of flavonolignans from Silybum marianum extract affords new minor constituents and preliminary structure-activity relationships.
(4/13)
NF-kappaB inhibitors from Brucea javanica exhibiting intracellular effects on reactive oxygen species.
(7/13)
AIM: Brucea javanica was studied to identify nuclear factor kappaB (NF-kappaB) inhibitors exhibiting reactive oxygen species (ROS) intracellular amplification. MATERIAL AND METHODS: Eight compounds were evaluated for selective cytotoxicity using HT-29, HeLa, and HL-60 cells, and in a NF-kappaB assay. Active compounds were then tested using ROS and mitochondria transmembrane potential (MTP) assays. NF-kappaB and nuclear factor activated T-cell (NFAT) translocation were also assessed using their respective whole cell assays. RESULTS: Bruceajavanone B, bruceantin, bruceine A, (-)-hydnocarpin, and chrysoeriol exhibited cytotoxic potential and NF-kappaB p65 inhibition. Chrysoeriol exhibited selective cytotoxicity against leukemia cells with greater potency and also showed an ability to up-regulate NFAT transcriptional pathways through the amplification of intracellular ROS, in the presence of H2O2, to a greater degree than bruceantin and bruceine. CONCLUSION: Chrysoeriol selectively kills leukemic cells and potentiates the amplification of ROS levels. Therefore, chrysoeriol could serve as a potential chemotherapeutic modifier for leukemia chemotherapy since leukemia cells have a higher susceptibility to elevated ROS levels. (+info)
Investigating the potential for toxicity from long-term use of the herbal products, goldenseal and milk thistle.
(8/13)