iridoids and Prostatic-Neoplasms

This study aims to develop and evaluate oleuropein loaded surface functionalized folate-targeted - PEG liposomes for the effective management of prostate cancer in an animal model.. Film hydration-cum-extrusion technique was used to produce liposomes. Particle size, entrapment efficiency, drug loading, electron microscopy, and drug release study were performed for the characterization. Cell viability and various in vitro studies (phosphatidylserine internalization, TUNEL assay, measurement of mitochondrial membrane potential and caspase-3 assay) were performed to compare the anticancer and apoptotic effects of developed liposomes against the plain oleuropein. Comparative pharmacokinetic profiling and anticancer efficacy studies including a change in tumor volume, body weight, and survival analysis were performed in mice model.. The developed liposomes (OL-FML) showed the particle size of 184.2 ± 9.16 nm, the zeta potential of 1.41 ± 0.24 mV, entrapment efficiency of 63.52 ± 4.15% and drug loading of 21.31 ± 2.37%. OL-FML showed higher in vitro anti-proliferative effect and apoptosis on 22Rv1 cells. In vivo pharmacokinetic study revealed a nearly 6 fold increase in the bioavailability of OL-FML (AUC. The study provides conclusive evidence for the utilization of combining passive and active targeting strategy to enhance the anticancer effect of OL.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Disease Models, Animal; Drug Liberation; Folic Acid; Humans; Iridoid Glucosides; Iridoids; Liposomes; Male; Mice; Mice, Inbred BALB C; Particle Size; Prostatic Neoplasms

Three new minor valepotriate isomers, jatamanvaltrates Z1 (1), Z2 (2), and Z3 (3), have been isolated from the whole plants of Valeriana jatamansi (syn. Valeriana wallichii.). Their structures were elucidated by extensive spectroscopic analysis, especially 2D NMR and ESI-MS/MS

Topics: Antineoplastic Agents, Phytogenic; Colonic Neoplasms; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Humans; Inhibitory Concentration 50; Iridoids; Isomerism; Male; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plant Roots; Prostatic Neoplasms; Valerian

Ten new valepotriates, jatamanvaltrates P-Y (1-10) and a known one, nardostachin (11), have been isolated from the whole plants of Valeriana jatamansi. The structures of the new compounds were determined by detailed spectroscopic data analysis. The isolated compounds were evaluated for cytotoxic activity against PC-3M cells, and a structure-activity relationship was examined for all the valepotriates isolated from V. jatamansi. The results highlighted the structure-activity relationship importance of the C-3-C-4 double bond, the oxirane ring, and the 10-chlorine in the valepotriates.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Humans; Iridoids; Magnetic Resonance Spectroscopy; Male; Molecular Structure; Prostatic Neoplasms; Structure-Activity Relationship; Valerian

Three new decomposition products of valepotriates, valtrals A-C (1-3), and two known products, baldrinal and homobaldrinal, are formed during the isolation procedure of the ethanol extract of the whole plants of Valeriana jatamansi. Their structures were determined by spectroscopic methods including IR, MS, 1D, and 2D NMR experiments. Compounds 1-3 showed selective cytotoxicity against metastatic prostate cancer (PC-3M) and colon cancer (HCT-8) cell lines.

Topics: Antineoplastic Agents, Phytogenic; Colonic Neoplasms; Drugs, Chinese Herbal; Humans; Iridoids; Male; Molecular Structure; Nardostachys; Nuclear Magnetic Resonance, Biomolecular; Prostatic Neoplasms; Valerian

To explore whether the inhibitory effect of Genipin on uncoupling protein-2 (UCP-2) in mitochondria is involved in energy metabolism of androgen-independent PC3 prostate cancer cells.. PC3 prostate cancer cells were cultured and treated with Genipin at the concentrations of 40, 80, and 160 μmol/L for 48 hours. Then the proliferation of the cells was detected by MTT assay, the expression of UCP-2 mRNA determined by RT-PCR, and the content of intracellular pyruvic acid (PA) and the activity of succinate dehydrogenase (SDH) in the mitochondria measured by visible spectrophotometry.. With the increased concentration of Genipin, the proliferative activity of the PC-3 cells, the expression level of UCP-2 mRNA, the content of intracellular PA and the activity of SDH in the cells were all decreased, namely, with the enhanced inhibitory effect of Genipin on UCP-2, a trend of reduction was observed in the proliferation of the cells, intracellular PA content, and SDH activity in the mitochondria.. Genipin is involved in the energy metabolism of androgen-independent PC3 prostate cancer cells by reducing the content of intracellular PA and the activity of SDH in the mitochondria, which may be associated with its inhibitory effect on UCP-2.

Topics: Cell Line, Tumor; Energy Metabolism; Humans; Ion Channels; Iridoids; Male; Mitochondria; Mitochondrial Proteins; Prostatic Neoplasms; Pyruvic Acid; RNA, Messenger; Succinate Dehydrogenase; Uncoupling Protein 2

Currently, there is increasing interest in the in vivo protective effects of natural antioxidants found in dietary plants against oxidative damage caused by free radical species. Oxidative stress has been invoked as a causative agent in cancer and epidemiological data suggest that the consumption of fruits and vegetables may be associated with a lower incidence of cancer. The fruit of the Olea europaea L. and olive oil contain hundreds of phytochemicals and its extracts have recently been shown to exhibit antioxidant properties, due to the action of oleuropein. In view of these considerations, in this study, we investigated the effects of oleuropein on LNCaP and DU145 prostate cancer cell lines and on BPH-1 non-malignant cells. Oleuropein reduces cell viability and induces thiol group modifications, γ-glutamylcysteine synthetase, reactive oxygen species, pAkt and heme oxygenase-1. Exposing cell cultures to oleuropein induces an antioxidant effect on BPH-1 cells and a pro-oxidant effect on cancer cells. Our results confirm the beneficial properties of olive oil and oleuropein, suggesting its possible use as an adjuvant agent in the treatment of prostatitis, in order to prevent the transformation of hypertrophic to cancerous cells.

Topics: Antineoplastic Agents; Antioxidants; Cell Line, Tumor; Cell Proliferation; Cell Survival; Glutamate-Cysteine Ligase; Heme Oxygenase-1; Humans; Iridoid Glucosides; Iridoids; L-Lactate Dehydrogenase; Male; Necrosis; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Pyrans; Reactive Oxygen Species; Sulfhydryl Compounds

The structures of 1,5-dihydroxy-3,8-epoxyvalechlorine (1a) and volvaltrate B (6a), two new chlorinated iridoids isolated from Valeriana jatamansi and V. officinalis, respectively, were originally assigned on the basis of spectroscopic methods. Reinvestigation using X-ray analysis and chemical transformation revealed that the original assignment of H-7 in 1a and OH-8 in 6a should be inverted and that the structures should be revised to 1 and 6, respectively. Correspondingly, the structure of valeriotetrate C (7a) should be revised to 7. Volvaltrate B (6) showed cytotoxic activity against the lung adenocarcinoma (A549), metastatic prostate cancer (PC-3M), colon cancer (HCT-8), and hepatoma (Bel7402) cell lines, with IC50 values of 8.5, 2.0, 3.2, and 6.1 μM, respectively.

Topics: Antineoplastic Agents, Phytogenic; Colonic Neoplasms; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Humans; Iridoids; Male; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plant Roots; Prostatic Neoplasms; Valerian

It has been reported that genipin, the aglycone of geniposide, induces apoptotic cell death in human hepatoma cells via a NADPH oxidase-reactive oxygen species (ROS)-c-Jun NH(2)-terminal kinase (JNK)-dependent activation of mitochondrial pathway. This continuing work aimed to define that mixed lineage kinase 3 (MLK3) is a key mediator, which connect between ROS and JNK in genipin-induced cell death signaling. In PC3 human prostate cancer cells, genipin stimulated MLK3 activity in concentration- and time-dependent manner. The PC3 cells stably transfected with dominant-negative form of MLK3 was less susceptible to population of the sub-G1 apoptotic cells, activation of caspase, collapse of mitochondrial membrane potential, and release of cytochrome c triggered by genipin, suggesting a crucial role of MLK3 in genipin signaling to apoptotic cell death. Diphenyleneiodonium (DPI), a specific inhibitor of NADPH oxidase, markedly inhibited ROS generation and MLK3 phosphorylation in the genipin-treated cells. Pretreatment with SP0600125, a specific inhibitor of JNK but neither U0126, a specific inhibitor of MEK1/2 nor PD169316, a specific inhibitor of p38 suppressed genipin-induced apoptotic cell death. Notably, both the phosphorylation of JNK and induction of c-Jun induced by genipin were markedly inhibited in PC3-EGFP-MLK3 (K144R) cells expressing a dominant-negative MLK3 mutant. Taken together, our observations suggest genipin signaling to apoptosis of PC3 cells is mediated via activation of ROS-dependent MLK3, which leads to downstream activation of JNK.

Topics: Apoptosis; Blotting, Western; Butadienes; Cell Line, Tumor; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors; Flow Cytometry; Green Fluorescent Proteins; Humans; Imidazoles; Iridoid Glycosides; Iridoids; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Kinase Kinases; Membrane Potential, Mitochondrial; Mitochondria; Mitogen-Activated Protein Kinase Kinase Kinase 11; Nitriles; Prostatic Neoplasms; Reactive Oxygen Species; Recombinant Fusion Proteins; Signal Transduction; Transfection

A new lignan glycoside, 1,5-dihydroxy-2-(4"-beta-D-glucopyranosyloxy-3"-methoxyphenyl)-6-(4'-hydroxy-3'-methoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, named ambrosidine ([structure: see text]), along with seven known compounds (four iridoids and three hydroxycinnamic esters) were isolated from the roots of Cephalaria ambrosioides. The structures of these compounds were determined by use of NMR and MS techniques and by chemical transformations. The cytotoxic activity of the novel compound [structure: see text] was evaluated against five human solid tumour cell lines.

Topics: Acetylation; Antineoplastic Agents, Phytogenic; Cell Survival; Colorectal Neoplasms; Drug Screening Assays, Antitumor; Glucosides; Greece; Humans; Hydrolysis; Iridoids; Lignans; Magnoliopsida; Male; Mass Spectrometry; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plant Roots; Plants, Medicinal; Prostatic Neoplasms; Tumor Cells, Cultured