iridoids and Colonic-Neoplasms

Hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) play important roles in cancer progression in various cancer cell lines. Although genipin, a constituent of Gardenia fruit, has been shown to have anti-tumor activity, its role in the suppression of HIF-1 and its downstream target genes is not well understood. We examined the effect of genipin on the intracellular level of HIF-1α and extracellular level of VEGF using the colon cancer cell line HCT116. We observed that genipin suppressed the accumulation of HIF-1α under hypoxia in various cancer cell lines, including HCT116, via the modulation of protein degradation. Genipin also suppressed the expression of VEGF and the invasion of colon cancer cells by blocking the extracellular signal-regulated kinase signaling pathway. Taken together, our results provide new insights into the potential role of genipin in suppressing colon cancer progression.

Topics: Cell Hypoxia; Colonic Neoplasms; Disease Progression; Extracellular Signal-Regulated MAP Kinases; HCT116 Cells; HT29 Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Iridoids; Neoplasm Invasiveness; Neoplasm Metastasis; Proteolysis; Proto-Oncogene Proteins c-akt; Vascular Endothelial Growth Factor A

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

To investigate the potentiation effect of Genipin to Cisplatin induced cell senescence in HCT-116 colon cancer cells in vitro.. Cell viability was estimated by Propidium iodide and Hoechst 3342, reactive oxygen species (ROS) with DHE, mitochondrial membrane potential (MMP) with JC-1 MMP assay Kit and electron current production with microbial fuel cells (MFC).. Genipin inhibited the UCP2 mediated anti-oxidative proton leak significantly promoted the Cisplatin induced ROS and subsequent cell death, which was similar to that of UCP2-siRNA. Cells treated with Cisplatin alone or combined with Genipin, ROS negatively, while MMP positively correlated with cell viability. Cisplatin induced ROS was significantly decreased by detouring electrons to MFC, or increased by Genipin combined treatment. Compensatory effects of UCP2 up-regulation with time against Genipin treatment were suggested. Shorter the Genipin treatment before Cisplatin better promoted the Cisplatin induced ROS and subsequent cell death.. The interaction of leaked electron with Cisplatin was important during ROS generation. Inhibition of UCP2-mediated proton leak with Genipin potentiated the cytotoxicity of Cisplatin. Owing to the compensatory effects against Genipin, shorter Genipin treatment before Cisplatin was recommended in order to achieve better potentiation effect.

Topics: Apoptosis; Bioelectric Energy Sources; Cell Proliferation; Cellular Senescence; Cisplatin; Colonic Neoplasms; Drug Synergism; HCT116 Cells; Humans; Iridoids; Membrane Potential, Mitochondrial; Oxidative Stress; Reactive Oxygen Species

Compounds that modulate cancer cell glucose metabolism could open new opportunities for antitumor therapy and for monitoring response using (18)F-FDG PET. Genipin, a natural dietary compound that blocks uncoupling protein 2 (UCP2)-mediated mitochondrial proton leakage, is a potential anticancer agent. We investigated the effect of genipin on glucose metabolism and the mitochondrial function of cancer cells.. Breast and colon cancer cells were assessed for effects of genipin on (18)F-FDG uptake. T47D breast cancer cells were further evaluated for time-dependent and dose-dependent effects on (18)F-FDG uptake, lactate release, oxygen consumption rate (OCR), reactive oxygen species (ROS) production, and mitochondrial membrane potential. The effects of UCP2 knockdown were evaluated using specific siRNA.. Cancer cells displayed significant reductions in (18)F-FDG uptake by genipin. T47D cells showed the greatest reduction to 32.6±1.0% of controls by 250μM genipin. The effect occurred rapidly, reaching a plateau by 1h that lasted up to 24h. The effect was dose-dependent with a half-inhibitory concentration of 60.8μM. An accompanying decrease in lactate release was consistent with reduced glycolytic flux. OCR was significantly decreased by genipin to 82.2±11.4% of controls, and ROS generation was increased to 156.7±16.0%. These effects were largely reproduced by UCP2 knockdown with specific siRNA.. Genipin decreased cancer cell (18)F-FDG uptake by reducing both glycolytic flux and mitochondrial oxidative respiration. This effect appeared to occur by blocking the ability of UCP2 to dissipate energy and restrict ROS production through proton leakage.

Topics: Biological Transport; Breast Neoplasms; Cell Line, Tumor; Colonic Neoplasms; Dose-Response Relationship, Drug; Fluorodeoxyglucose F18; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Glucose; Humans; Iridoids; Lactic Acid; Matrix Metalloproteinases; Reactive Oxygen Species; RNA, Small Interfering; Signal Transduction; Time Factors; Uncoupling Protein 2

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

Crude phenolic extracts (PE) have been obtained from naturally bearing Spanish extra-virgin olive oil (EVOO) showing different polyphenol families such as secoiridoids, phenolic alcohols, lignans, and flavones. EVOO-derived complex phenols (especially from the Arbequina variety olive) have been shown to suppress cell growth of SW480 and HT29 human colon adenocarcinoma cell lines. Inhibition of proliferation by EVOO-PE Arbequina variety extract was accompanied by apoptosis in both colon-cancer-cell lines and a limited G₂M cell-cycle arrest in the case of SW480 cells. The metabolized compounds from EVOO-PE in culture medium and cytoplasm of both cell lines were analyzed using nano-liquid chromatography (nanoLC) coupled with electrospray ionization-time-of-flight-mass spectrometry (ESI-TOF-MS). The results showed many phenolic compounds and their metabolites both in the culture medium as well as in the cytoplasm. The main compounds identified from EVOO-PE were hydroxylated luteolin and decarboxymethyl oleuropein aglycone.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; Biotransformation; Cell Proliferation; Chromatography, Liquid; Colonic Neoplasms; Culture Media, Conditioned; Cytoplasm; Decarboxylation; G2 Phase Cell Cycle Checkpoints; HT29 Cells; Humans; Hydroxylation; Iridoid Glucosides; Iridoids; Luteolin; Metabolomics; Nanotechnology; Olive Oil; Phenols; Plant Oils; Pyrans; Spectrometry, Mass, Electrospray Ionization

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

The herb of Oldenlandia diffusa (Willd.) Roxb. (Family Rubiaceae) is well-known in Chinese folk medicine for the treatment of hepatitis and malignant tumors of the liver, lung and stomach. However, another herb of O. corymbosa (L.) Lam is also used interchangeably in South China for treating the same conditions. To compare the efficacy of the two herbs, the antiproliferative effect of their extracts and the antiangiogenic activity of their main constituents were appraised. The Sulforhodamine B (SRB) assay in human hepatoma HepG2 cells and human colon carcinoma CaCo2 cells and the zebrafish angiogenic model were used for this purpose. The results showed almost no antiproliferative effect of the methanol extracts from O. diffusa and O. corymbosa, while the chloroform extracts exhibited slightly antiproliferative effects. The main components had almost no effect on zebrafish angiogenic vessel formation at the concentrations tested. The results suggest that the mechanism of antitumor activity of O. diffusa may not be attributed to the antiproliferative and antiangiogenic effects.

Topics: Adenocarcinoma; Angiogenesis Inhibitors; Animals; Caco-2 Cells; Cell Line, Tumor; Cell Proliferation; Chromatography, High Pressure Liquid; Colonic Neoplasms; Cyclopentane Monoterpenes; Glucosides; Humans; Iridoids; Oldenlandia; Oleanolic Acid; Phytotherapy; Plant Extracts; Pyrans; Zebrafish