fucoxanthin and Prostatic-Neoplasms

The exploration of natural preventive molecules for nutraceutical and pharmaceutical use has recently increased. In this scenario, marine microorganisms represent an underestimated source of bioactive products endowed with beneficial effects on health that include anti-oxidant, anti-inflammatory, differentiating, anti-tumor, and anti-angiogenic activities. Here, we tested the potential chemopreventive and anti-angiogenic activities of an extract from the marine coastal diatom

Topics: Carotenoids; Diatoms; Endothelial Cells; Humans; Male; Plant Extracts; Prostatic Neoplasms; Xanthophylls

To investigate the apoptosis- inducing effect of fucoxanthin in human prostate cancer PC-3 cells and the underlying mechanism.. Fucoxanthin significantly inhibited the viability of PC-3 cells in a time- and dose-dependent manner, and dose-dependently induced apoptosis of the cells (. Fucoxanthin induces apoptosis of PC-3 cells by triggering mitochondrial dysfunction to cause oxidative stress and by activating mitochondria-mediated apoptotic signaling pathways, suggesting its potential in prostate cancer treatment.

Topics: Apoptosis; bcl-2-Associated X Protein; Humans; Hydrogen Peroxide; Male; Membrane Potential, Mitochondrial; Mitochondria; Oxidative Stress; PC-3 Cells; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Xanthophylls

To develop a high-throughput screening system to measure the conversion of testosterone to dihydrotestosterone (DHT) in cultured human prostate cancer cells using turbulent flow chromatography liquid chromatography-triple quadrupole mass spectrometry (TFC-LC-TQMS).. After optimizing the cell reaction system, this method demonstrated a screening capability of 103 samples, including 78 single compounds and 25 extracts, in less than 12 h without manual sample preparation. Consequently, fucoxanthin, phenethyl caffeate, and Curcuma longa L. extract were validated as bioactive chemicals that inhibited DHT production in cultured DU145 cells. In addition, naringenin boosted DHT production in DU145 cells.. The method can facilitate the discovery of bioactive chemicals that modulate the DHT production, and four phytochemicals are potential candidates of nutraceuticals to adjust DHT levels in male hormonal dysfunction.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Chromatography, Liquid; Dihydrotestosterone; Drug Discovery; Flavanones; High-Throughput Screening Assays; Humans; Male; Mass Spectrometry; Plant Extracts; Prostatic Neoplasms; Testosterone; Xanthophylls

The antitumor effect of fucoxanthin, a marine carotenoid found in brown algae, was investigated on prostate cancer cells.. LNCap prostate cancer cells were treated with fucoxanthin and the effects were evaluated in relation to cell proliferation, cell cycle, expression of growth arrest, DNA damage-inducible protein (GADD45) genes, and phosphorylation status of mitogen-activated protein kinases.. Fucoxanthin inhibited the growth of LNCap prostate cancer cells in a dose-dependent manner. Growth-inhibitory effects were accompanied by the induction of GADD45A expression and G(1) cell cycle arrest, but not apoptosis. Furthermore, fucoxanthin activated c-Jun N-terminal kinase (SAPK/JNK), while the inhibition of SAPK/JNK attenuated the induction of G(1) arrest and GADD45A expression by fucoxanthin.. These results show that fucoxanthin induces G(1) cell cycle arrest in prostate cancer cells, and suggest that ADD45A and SAPK/JNK might be involved in these effects.

Topics: Base Sequence; Cell Cycle Proteins; Cell Line, Tumor; DNA Primers; Dose-Response Relationship, Drug; Enzyme Activation; G1 Phase; Humans; Male; Mitogen-Activated Protein Kinase Kinases; Nuclear Proteins; Polymerase Chain Reaction; Prostatic Neoplasms; Xanthophylls

Neoxanthin and fucoxanthin, which have the characteristic structure of 5,6-monoepoxide and an allenic bond, were previously found to reduce the viability of human prostate cancer cells most intensively among 15 dietary carotenoids tested. In the present study, the induction of apoptosis in PC-3 cells by these two carotenoids was characterized by morphological changes, DNA fragmentation, an increased percentage of hypodiploid cells, and cleavages of caspase-3 and PARP. The ratio of apoptotic cells reached more than 30% after treatment for 48 h with 20 microM carotenoids. They reduced the expression of Bax and Bcl-2 proteins, but not Bcl-X(L). Fucoxanthin accumulated in the cells at the same level as neoxanthin. Moreover, fucoxanthinol, a deacetylated product of fucoxanthin, formed in the cells treated with fucoxanthin and reached a level comparable to that of fucoxanthin after incubation for 24 h. Treatment by fucoxanthinol alone also induced apoptosis in PC-3 cells. Thus, neoxanthin and fucoxanthin treatments were found to induce apoptosis through caspase-3 activation in PC-3 human prostate cancer cells.

Topics: Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Carotenoids; Humans; Male; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Tumor Cells, Cultured; Xanthophylls

Fucoxanthin, a major carotenoid in edible brown algae, potentially inhibits the proliferation of human prostate cancer cells via apoptosis induction. However, it has been postulated that dietary fucoxanthin is hydrolyzed into fucoxanthinol in the gastrointestinal tract before absorption in the intestine. In the present study, we investigated the further biotransformation of orally administered fucoxanthin and estimated the cytotoxicity of fucoxanthin metabolites on PC-3 human prostate cancer cells. After the oral administration of fucoxanthin in mice, two metabolites, fucoxanthinol and an unknown metabolite, were found in the plasma and liver. The unknown metabolite was isolated from the incubation mixture of fucoxanthinol and mouse liver preparation (10,000 g supernatant of homogenates), and a series of instrumental analyses identified it as amarouciaxanthin A [(3S,5R,6'S)-3,5,6'-trihydroxy-6,7-didehydro-5,6,7',8'-tetrahydro-beta,epsilon-carotene-3',8'-dione]. The conversion of fucoxanthinol into amarouciaxanthin A was predominantly shown in liver microsomes. This dehydrogenation/isomerization of the 5,6-epoxy-3-hydroxy-5,6-dihydro-beta end group of fucoxanthinol into the 6'-hydroxy-3'-oxo-epsilon end group of amarouciaxanthin A required NAD(P)+ as a cofactor, and the optimal pH for the conversion was 9.5 to 10.0. Fucoxanthinol supplemented to culture medium via HepG2 cells was also converted into amarouciaxanthin A. The 50% inhibitory concentrations on the proliferation of PC-3 human prostate cancer cells were 3.0, 2.0, and 4.6 microM for fucoxanthin, fucoxanthinol, and amarouciaxanthin A, respectively. To our knowledge, this is the first report on the enzymatic dehydrogenation of a 3-hydroxyl end group of xanthophylls in mammals.

Topics: Administration, Oral; Animals; Antineoplastic Agents; beta Carotene; Cell Division; Cell Line, Tumor; Humans; In Vitro Techniques; Male; Mice; Microsomes, Liver; Prostatic Neoplasms; Xanthophylls