Analysis of sitosteryl oleate esters in phytosterols esters enriched foods by HPLC-ESI-MS(2.).

Phytosteryl esters (PE)-enriched spreads are marketed for eating and cooking purposes. Temperature and also light exposure are the major factors leading to the formation of PE oxides in food matrix. In this study a high-speed HPLC-MS(2) method was developed to analyze the major PE present in PE-enriched spreads: sitosteryl oleate (SO) and its oxidation products, by using synthesized compounds as standards.

Methanolic extract of white asparagus shoots activates TRAIL apoptotic death pathway in human cancer cells and inhibits colon carcinogenesis in a preclinical model.

Shoots of white asparagus are a popular vegetable dish, known to be rich in many bioactive phytochemicals reported to possess antioxidant, and anti-inflammatory and antitumor activities. We evaluated the anticancer mechanisms of a methanolic extract of Asparagus officinalis L. shoots (Asp) on human colon carcinoma cells (SW480) and their derived metastatic cells (SW620), and Asp chemopreventive properties were also assessed in a model of colon carcinogenesis.

Epigenetic effects of the natural flavonolignan silibinin on colon adenocarcinoma cells and their derived metastatic cells.

Epigenetic modifications are important in tumorigenesis. The most frequent epigenetic phenomena in cancer are histone deacetylation and DNA hypermethylation, which lead to gene silencing, particularly of tumor suppressor genes. However, monotherapies with histone deacetylase (HDAC) or DNA methyltransferase (DNMT) inhibitors lack efficacy, hence there is a need to enhance their anticancer action in a safe and effective combination therapy.

Apple procyanidins affect several members of the ErbB receptor tyrosine kinase family in vitro.

Complex polyphenol-rich extracts from apples are known to inhibit the activity of the epidermal growth factor receptor (EGFR) in vitro. The aim of the present study was to identify the bioactive constituents of the apple juice extract which contribute substantially to this potentially chemopreventive effect and to address the question whether the effect is specific to the EGFR or whether other members of the ErbB-receptor family might also be affected. Apple-derived dihydrochalcones and their respective glycosides were found to decrease EGFR activity under cell-free conditions with IC50-values ranging from 0.

Silibinin inhibits tumor growth in a murine orthotopic hepatocarcinoma model and activates the TRAIL apoptotic signaling pathway.

Aim: The present study investigated the molecular mechanism of silibinin-induced antitumoral effects in hepatocarcinoma Hep-55.1C cells in vitro and in a hepatocarcinoma model in mice.

Materials And Methods: Cell death was analyzed by flow cytometry.

Silibinin, a natural flavonoid, modulates the early expression of chemoprevention biomarkers in a preclinical model of colon carcinogenesis.

The flavonolignan silibinin, the major biologically active compound of the milk thistle (Silybum marianum), has been shown to possess anticancer properties in a variety of epithelial cancers. The present study investigated the potential of silibinin as a chemopreventive agent in colon carcinogenesis. The rat azoxymethane (AOM)-induced colon carcinogenesis model was used because of its molecular and clinical similarities to sporadic human colorectal cancer.

The flavonolignan silibinin potentiates TRAIL-induced apoptosis in human colon adenocarcinoma and in derived TRAIL-resistant metastatic cells.

Silibinin, a flavonolignan, is the major active component of the milk thistle plant (Silybum marianum) and has been shown to possess anti-neoplastic properties. TNF-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent which selectively induces apoptosis in cancer cells. However, resistance to TRAIL-induced apoptosis is an important and frequent problem in cancer treatment.

Silibinin triggers apoptotic signaling pathways and autophagic survival response in human colon adenocarcinoma cells and their derived metastatic cells.

Silibinin, a flavonolignan isolated from the milk thistle plant (Silybum marianum), possesses anti-neoplastic properties. In vitro and in vivo studies have recently shown that silibinin inhibits the growth of colorectal cancer (CRC). The present study investigates the mechanisms of silibinin-induced cell death using an in vitro model of human colon cancer progression, consisting of primary tumor cells (SW480) and their derived metastatic cells (SW620) isolated from a metastasis of the same patient.

Implication of NF-κB and p53 in the expression of TRAIL-death receptors and apoptosis by apple procyanidins in human metastatic SW620 cells.

Introduction: The nuclear factor-kappaB (NF-NF-κ) has been shown to upregulate pro-apoptotic mediators such as TRAIL-DR4/-DR5 receptors and the p53 transcription factor depending on the type of stimulus and the cell type involved. Previously, apple procyanidins (Pcy) have been shown to upregulate the expression of TRAIL-DR4/-DR5 and thereby overcoming the resistance of human colon cancer-derived metastatic SW620 cells to TRAIL.

Objectives: NF-κB and p53 were investigated for their involvement in the Pcy-triggered apoptosis of human derived-metastatic colon cancer (SW620) cells.

Lupulone triggers p38 MAPK-controlled activation of p53 and of the TRAIL receptor apoptotic pathway in human colon cancer-derived metastatic cells.

We previously reported that the chemopreventive agent lupulone induces apoptosis through activation of the extrinsic pathway via TRAIL DR4/DR5 death receptors overcoming SW620 cell resistance to TRAIL. However, the underlying molecular mechanisms remain unknown. Since the mitogen-activated protein kinases (MAPKs), Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 control fundamental cellular processes such as apoptosis, we determined the role of these MAPKs in lupulone-triggered apoptosis.

Early modulation of gene expression used as a biomarker for chemoprevention in a preclinical model of colon carcinogenesis.

By using the rat azoxymethane (AOM)-induced colon carcinogenesis model, which mirrors many clinical features of human colorectal cancer, we examined whether genetic changes occurring early in colonic mucosa are predictive of treatment efficacy. In the present study the administration of the chemopreventive agent lupulone over the course of 7 weeks postinitiation reduced the number of preneoplastic lesions in the colonic mucosa by 50%. At the molecular level we observed the downregulation of genes involved in the inflammatory response, including IL-1β and TNF-α, and of matrix metalloproteinase-7 gene and protein expression.

p53 Activates Either Survival or Apoptotic Signaling Responses in Lupulone-Treated Human Colon Adenocarcinoma Cells and Derived Metastatic Cells.

The SW480 cell line is derived from a human colon adenocarcinoma, and SW620 cells are derived from a lymph node metastasis of the same patient. We have previously shown that lupulone induces apoptosis in SW480 cells, through a cross talk between the TRAIL-death receptor pathway and the mitochondrial apoptotic pathway. In SW620 cells, lupulone induced apoptosis only through TRAIL-death receptor activation.

Identification of gene expression profiles correlated to tumor progression in a preclinical model of colon carcinogenesis.

The rat azoxymethane (AOM)-induced colon carcinogenesis model provides useful information for understanding human colorectal neoplasia. Here, we used the AOM model to measure the gene expression profiles of biomarkers related to tumor progression. We assessed tumor progression stages by computed tomographic (CT) colonography.

Long-term administration of aspirin inhibits tumour formation and triggers anti-neoplastic molecular changes in a pre-clinical model of colon carcinogenesis.

Despite numerous studies aimed at verifying the anti-tumour activity of aspirin on colon carcinogenesis little is known on the molecular targets involved in the anti-carcinogenic properties of this drug. We investigated the long-term administration of low dose of aspirin in a model of experimental colon carcinogenesis in rats. Adult Wistar rats received an intraperitoneal injection of azoxymethane (AOM) once a week for two weeks in order to initiate colon carcinogenesis.

Apple procyanidins activate apoptotic signaling pathway in human colon adenocarcinoma cells by a lipid-raft independent mechanism.

Flavonoids are polyphenolic compounds able to favour cholesterol-lipid-raft formation and control cell signaling pathways by targeting receptors at the cell surface. Procyanidins (Pcy) are oligomeric and polymeric flavonoids formed by catechins and epicatechins monomers trigger apoptosis by activating TRAIL-death receptors in human colon adenocarcinoma SW480 cells. Here, we investigated whether the apoptotic process triggered by apple procyanidins involving the up-regulation of TRAIL-death receptors DR4/DR5 at the cell surface was dependent on cell membrane lipid-raft formation.

Effects of oxidation on the hydrolysis by cholesterol esterase of sitosteryl esters as compared to a cholesteryl ester.

Phytosteryl esters (PE) are used as ingredients in functional food to decrease plasma concentration of low density lipoprotein-cholesterol (LDL-C). Effective impairment of cholesterol absorption by PE suggests that these esters are hydrolyzed by the pancreatic cholesterol esterase (CEase, EC 3.1.

Lupulone, a hop bitter acid, activates different death pathways involving apoptotic TRAIL-receptors, in human colon tumor cells and in their derived metastatic cells.

Our study aimed to compare death signalling pathways triggered by lupulone in TRAIL-sensitive human colon cancer cells (SW480) and in their derived TRAIL-resistant metastatic cells (SW620). Lupulone (40 microg/ml) up-regulated expression of TRAIL DR4/DR5 death receptors at the cell surface of both cell lines, even in the absence of exogenous TRAIL ligand. Cell death induced by lupulone was inhibited in SW480 and SW620 cells exposed to blocking anti-DR4/DR5 antibodies.

Synthesis of highly pure oxyphytosterols and (oxy)phytosterol esters. Part II. (Oxy)-sitosterol esters derived from oleic acid and from 9,10-dihydroxystearic acid [1].

Several efficient synthetic routes giving readily access to (oxy)-sitosterol esters and (oxy)-cholesterol esters derived respectively from oleic acid and from 9,10-dihydroxystearic acid were developed for the first time. This approach allowed that sufficient amounts of the latter were available in order to carry out further biological studies.

Synthesis of highly pure oxyphytosterols and (oxy)phytosterol esters Part I. Regioselective hydrogenation of stigmasterol: an easy access to oxyphytosterols.

The synthesis of several oxyphytosterols is described starting from stigmasterol, the key step being the regioselective hydrogenation of the 22-23 double bond of the latter.

Antiangiogenic properties of lupulone, a bitter acid of hop cones.

Background: Angiogenesis is the result of intricate steps regulated by the balance between agonistic and antagonistic effectors. Disturbance of this balance leads to an 'angiogenic' switch critical for tumor development.

Materials And Methods: Using human umbilical vein endothelial cells (HUVEC) the effects of lupulone were analyzed on proliferation induced by angiogenic growth factors, transmembrane cell migration toward fibronectin and formation of a network of tubular-like structures on Matrigel.

Polyamines and the intestinal tract.

Owing to their high turnover, the intestinal mucosal cells have a particularly high requirement for polyamines. Therefore, they are an excellent charcol for the study of polyamine function in rapid physiological growth and differentiation. After a cursory introduction to the major aspects of polyamine metabolism, regulation, and mode of action, we discuss the contribution of the polyamines to the maintenance of normal gut function, the maturation of the intestinal mucosa, and its repair after injuries.

Follow-up of tumor development in the colons of living rats and implications for chemoprevention trials: assessment of aspirin-difluoromethylornithine combination.

We aimed to establish a reliable procedure allowing the follow-up of tumor development by computed tomographic (CT) colonography in an animal model of colon carcinogenesis in order to assess the chemopreventive efficacy of aspirin and difluoromethylornithine (DFMO) given in combination. Fischer rats received an intraperitoneal injection (25 mg/kg) of dimethylhydrazine (DMH) once a week for two weeks in order to initiate colon carcinogenesis. Five months after the last injection of DMH, a first CT colonography was performed and rats were then randomly separated into two groups (control and experimental).

Chemopreventive effects of lupulone, a hop {beta}-acid, on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis.

The bitter acids of hops (Humulus lupulus L.) mainly consist of humulones or alpha-acids and lupulones or beta-acids. We aimed to evaluate the antiproliferative mechanisms of lupulones on a human metastatic colon carcinoma-derived cell line (SW620 cells) and to assess their chemopreventive effects in a model of colon carcinogenesis.

Mitochondrial perturbation, oxidative stress and lysosomal destabilization are involved in 7beta-hydroxysitosterol and 7beta-hydroxycholesterol triggered apoptosis in human colon cancer cells.

We reported previously that 7beta-hydroxysitosterol and 7beta-hydroxycholesterol induced apoptosis in Caco-2 cells. Apoptosis caused by 7beta-hydroxysitosterol but not by 7beta-hydroxycholesterol was related to a caspase-dependent process. In the present report, we compared the effects of both compounds on mitochondria integrity and on various modulators of apoptosis.

Synergism between apple procyanidins and lysosomotropic drugs: potential in chemoprevention.

Background: Procyanidins are apple constituents with potential in colon cancer chemoprevention.

Materials And Methods: Human colon cancer derived metastatic cells (SW620), growing under standardized conditions, were exposed to procyanidins and lysosomotropic compounds. Growth, apoptosis and lysosomal integrity was determined using published methods.