pectins and Pancreatic-Neoplasms

Pancreatic carcinoma ranks as the eighth most frequent type of solid tumour arising worldwide yet it represents the fourth most frequent cause of death. This discrepancy reflects the current lack of effective treatment available for the pancreatic cancer patient and highlights the urgent need for new therapeutic principles in this area. The last five years have seen an increasing number of novel approaches both in the pre-clinical area as well as in clinical trials for pancreatic cancer treatments. This review summarizes these new developments and attempts to rationalize the possibilities available for the patient at the beginning of the new millennium.

Topics: Adjuvants, Immunologic; Antibodies, Monoclonal; Antineoplastic Agents; Bile; Biotransformation; Cancer Vaccines; Carcinoma; Clinical Trials as Topic; Cytochrome P-450 CYP2B1; Cytosine; Deoxycytidine; Dioxolanes; DNA, Antisense; Endopeptidases; Enzyme Inhibitors; Gemcitabine; Genes, p53; Genes, ras; Genetic Therapy; Heat-Shock Proteins; Humans; Ifosfamide; Multicenter Studies as Topic; Neoplasm Proteins; Neoplastic Stem Cells; Pancreatic Neoplasms; Pectins; Pilot Projects; Polyamines; Prospective Studies; Prostheses and Implants; Sesquiterpenes; Spiro Compounds; Tissue Extracts; Topoisomerase I Inhibitors

This study intends to investigate the inhibitory potential of different plant derived saccharides on cell migration and adhesion of pancreatic ductal adenocarcinoma (PDAC) cells to microvascular liver endothelium, particularly considering the role of transmembranous galectin-3. PDAC cell lines PancTu1 and Panc1 were characterized by considerable (transmembranous) galectin-3 (Gal3) expression. SiRNA mediated Gal3 knockdown as well as treatment with differentially processed pectins and arabinogalactan-proteins (AGPs) did not impact on cell migration of either PDAC cell line. In contrast, Gal3 knockdown reduced adhesion of PDAC cells to the liver endothelial cell line TMNK-1 being more pronounced in Panc1 cells. Similarly, plant derived substances did not impact cell adhesion of PancTu1 cells while partially hydrolyzed citrus pectin (MCP), pectinase-treated MCP (MCP

Topics: Blood Proteins; Carcinoma, Pancreatic Ductal; Cell Adhesion; Cell Line, Tumor; Cell Proliferation; Cell Survival; Citrus; Galectin 3; Galectins; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Mucoproteins; Neoplasm Metastasis; Pancreatic Neoplasms; Pectins; Plant Proteins

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant carcinomas, which is characterized by apoptosis- and autophagy-dependent tumorigenic growth. Autophagy constitutes a stress adaptation that suppresses apoptosis. To explore new leading compound against PDAC, a pectin-like polysaccharide named RP02-1, was purified from roots of Polygala tenuifolia. Bioactivity test showed that RP02-1 might inhibit pancreatic cancer cells growth in vitro and in vivo. RP02-1 could inhibit pancreatic cancer cell (AsPC-1 and BxPC-3) proliferation, migration and colony formation. Mechanism study suggested that RP02-1 induced pancreatic cancer cells apoptosis, which was detected by Bcl-2 down-regulation, Bax up-regulation and conversion from Caspase 3 to Cleaved Caspase 3. Interestingly, autophagy was suppressed by RP02-1 treatment concentration-dependently through affenuatingBeclin-1, ATG5 and LC3B expression in BxPC-3 cells. In addition, RP02-1 could inhibit autophagy induced by Pennogenin 3-O-beta-chacotrioside. However, RP02-1 had almost no toxicity both in vitro and in vivo. The above results suggested that RP02-1 might be a potential leading compound for new drug candidate development for human PDAC treatment via inducing apoptosis and against autophagy.

Topics: Animals; Apoptosis; Autophagy; Caspase 3; Cell Line, Tumor; Cell Movement; Cell Proliferation; Humans; Immunohistochemistry; Mice, Inbred BALB C; Mice, Nude; Pancreatic Neoplasms; Pectins; Polygala; Polysaccharides; Xenograft Model Antitumor Assays

Crude polysaccharides were obtained from fruits of Lycium ruthenicum Murr using hot water extraction followed by ethanol precipitation. A homogeneous polysaccharide, LRP3-S1 with a relative molecular weight of 114.8 kDa was purified by anion-exchange chromatography on DEAE Sepharose

Topics: Antineoplastic Agents; Carbohydrate Conformation; Carcinoma, Pancreatic Ductal; Cell Line; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Lycium; Pancreatic Neoplasms; Pectins; Structure-Activity Relationship