dihydrogenistin and Prostatic-Neoplasms

In human prostate cancer cells, the availability of the steroid hormone 1,25-dihydroxyvitamin D(3) for antimitotic action is determined through the activity of the two enzymes CYP24 and CYP27B1, viz. 25-hydroxyvitamin D-24-hydroxylase and 25-hydroxyvitamin D-1alpha-hydroxylase. High performance liquid chromatography (HPLC) analysis of [(3)H]25(OH)D(3) metabolism in human prostate cancer DU-145 cells revealed that genistein and other isoflavonoids, such as dihydrogenistein and daidzein, as well as the antiestrogenic compound ICI 182,780, inhibited Vitamin D-metabolizing enzyme activities. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that only in case of genistein this was due to transcriptional inhibition of CYP24 and CYP27B1 gene expressions. In case of CYP27B1, reduction of gene activity involves histone deacetylation because genistein was inactive in the presence of the histone deactylase inhibitor trichostatin A. In contrast, under the same condition, CYP24 gene activity was largely suppressed. In summary, our results suggest that a combined effect of genistein and trichostatin A could increase the responsiveness of human prostate cancer cells to the antiproliferative action of 1,25-dihydroxyvitamin D(3).

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Cell Division; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Estradiol; Estrogen Antagonists; Estrogens, Non-Steroidal; Fulvestrant; Genistein; Histone Deacetylases; Humans; Hydroxamic Acids; Isoflavones; Male; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Steroid Hydroxylases; Time Factors; Transcription, Genetic; Tumor Cells, Cultured; Vitamin D; Vitamin D3 24-Hydroxylase

Chemical investigation of a soybean phytochemical concentrate resulted in the isolation and identification of two new isoflavanones, dihydrodaidzin (1) and dihydrogenistin (2), a new isoflavone, 2' ',6' '-O-diacetyloninin (3), and two new triterpenoid saponins (13 and 14). Nine known isoflavonoids (4-12) and three known saponins (15-17) were also identified. Structures of the new compounds were established by a combination of extensive NMR (DEPT, DQF-COSY, HMBC, HMQC, and ROESY) studies and chemical degradation. Cytotoxic activities (ED(50)) of various extracts and selected isoflavonoids and saponins were measured against human stomach carcinoma (Hs 740.T, Hs 756 T), breast adenocarcinoma (Hs 578 T, Hs 742.T), and prostate carcinoma (DU 145, LNCaP-FGC) cell lines. Isoflavonoids 3 and 5 were more active than 1 and 2 versus at least one of the three cell lines examined, indicating the importance of the 2,3-double bond in cytotoxicity. Saponins 13, 14, and 15 were slightly more active than saponins 16 and 17, indicating that sugar attachments at position-22 enhance cytotoxic activity.

Topics: Breast Neoplasms; Drug Screening Assays, Antitumor; Female; Glycine max; Humans; Hydrolysis; Inhibitory Concentration 50; Isoflavones; Male; Nuclear Magnetic Resonance, Biomolecular; Plants, Medicinal; Prostatic Neoplasms; Saponins; Stereoisomerism; Stomach Neoplasms; Structure-Activity Relationship; Triterpenes; Tumor Cells, Cultured