Xanthohumol, a prenylflavonoid derived from hops induces apoptosis and inhibits NF-kappaB activation in prostate epithelial cells
ABSTRACT There is increasing evidence that certain natural compounds found in plants may be useful as cancer chemopreventive or chemotherapeutic agents. Limited in vitro studies indicate that several prenylated flavonoids present in the hop plant (Humulus lupulus) possess anticarcinogenic properties. The purpose of this study was to investigate the anti-tumorigenic effects of xanthohumol (XN), the major prenylflavonoid in hops, on prostate cancer and benign prostate hyperplasia. BPH-1 and PC3 cell lines were used in our study to represent both non-tumorigenic hyperplasia and malignant prostate cancer. In both BPH-1 and PC3 cells, XN and its oxidation product, XAL, decreased cell viability in a dose dependent manner (2.5-20 microM) as determined by MTT assay and caused an increase in the formation of early and late apoptotic cells as determined by Annexin V staining and multicaspase assays. XN and its oxygenated derivative also induced cell cycle changes in both cells lines, seen in an elevated sub G1 peak at 48h treatment. Western blot analysis was performed to confirm the activation of proapoptotic proteins, Bax and p53. XN and its derivative caused decreased activation of NFkappaB. This work suggests that XN and its oxidation product, XAL, may be potentially useful as a chemopreventive agent during prostate hyperplasia and prostate carcinogenesis, acting via induction of apoptosis and down-regulation of NFkappaB activation in BPH-1 cells.
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ABSTRACT: Ethanol-mediated free radical generation is directly involved in alcoholic liver disease. In addition, chronic alcohol binging also induces pathological changes and dysfunction in multi-organs. In the present study, the protective effect of Xanthohumol (XN) on ethanol-induced damage was evaluated by determining antioxidative parameters and stress oxidative markers in liver, kidney, lung, heart and brain of rats. An acute treatment (4 g/kg b.w.) of ethanol resulted in the depletion of superoxide dismutase, catalase and glutathione S transferase activities and reduced glutathione content. This effect was accompanied by the increased activity of tissue damage marker enzymes (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and lactate dehydrogenase) and a significant increase in lipid peroxidation and hydrogen peroxide concentrations. Pre-treatment with XN protected rat tissues from ethanol-induced oxidative imbalance and partially mitigated the levels to nearly normal levels in all tissues checked. This effect was dose dependent, suggesting that XN reduces stress oxidative and protects rat tissues from alcohol-induced injury.Toxicology Reports 01/2014; 1. DOI:10.1016/j.toxrep.2014.09.004
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ABSTRACT: Microbial transformation of xanthohumol isolated from agro-residue (spent hops), by Aspergillus ochraceus was investigated. A new aurone, (Z)-2″-(2‴-hydroxyisopropyl)-dihydrofurano[4″,5″:6,7]-3',4'-dihydroxy-4-methoxyaurone, was obtained as a main transformation product. Three minor metabolites were identified as 2″-(2‴-hydroxyisopropyl)-dihydrofurano[4″,5″:3',4']-2',4-dihydroxy-6'-methoxychalcone, (2S,2″S)-2″-(2‴-hydroxyisopropyl)-dihydrofurano[4″,5″:7,8]-4'-hydroxy-5-methoxyflavanone and (2S,2″R)-2″-(2‴-hydroxyisopropyl)-dihydrofurano[4″,5″:7,8]-4'-hydroxy-5-methoxyflavanone. Their structures were elucidated on the basis of spectroscopic evidences. The antioxidant properties of xanthohumol and its metabolites were investigated using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. The major biotransformation product, was 8.6-fold stronger antioxidant than xanthohumol and 2.3-fold than ascorbic acid.Journal of Basic Microbiology 01/2014; 54(1). DOI:10.1002/jobm.201200320 · 1.20 Impact Factor
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ABSTRACT: Health beneficial effects of xanthohumol have been reported, and basic research provided evidence for anti-cancer effects. Furthermore, xanthohumol was shown to inhibit the migration of endothelial cells. Therefore, this study investigated the anti-metastatic potential of xanthohumol. MCF-7 breast cancer spheroids which are placed on lymphendothelial cells (LECs) induce "circular chemorepellent-induced defects" (CCIDs) in the LEC monolayer resembling gates for intravasating tumour bulks at an early step of lymph node colonisation. NF-κB reporter-, EROD-, SELE-, 12(S)-HETE- and adhesion assays were performed to investigate the anti-metastatic properties of xanthohumol. Western blot analyses were used to elucidate the mechanisms inhibiting CCID formation. Xanthohumol inhibited the activity of CYP, SELE and NF-kB and consequently, the formation of CCIDs at low micromolar concentrations. More specifically, xanthohumol affected ICAM-1 expression and adherence of MCF-7 cells to LECs, which is a prerequisite for CCID formation. Furthermore, markers of epithelial-to-mesenchymal transition (EMT) and of cell mobility such as paxillin, MCL2 and S100A4 were suppressed by xanthohumol. Xanthohumol attenuated tumour cell-mediated defects at the lymphendothelial barrier and inhibited EMT-like effects thereby providing a mechanistic explanation for the anti-intravasative/anti-metastatic properties of xanthohumol.Archives of Toxicology 03/2013; DOI:10.1007/s00204-013-1028-2 · 5.08 Impact Factor