pectins and Ovarian-Neoplasms

Here we sought to determine the relationship between STAT3 activity and Galectin-3 (Gal-3) and to investigate the cytotoxic effect of PectaSol-C Modified Citrus Pectin (Pect-MCP) as a specific competitive inhibitor of Galectin-3 (Gal-3) in combination with Paclitaxel (PTX) to kill the ovarian cancer cell SKOV-3 multicellular tumor spheroid (MCTS). To this order, SKOV-3 cells in 2D and 3D cultures were treated with exogenous Gal-3 for the assessment of STAT3 activity. Two-way ANOVA main effect and IC

Topics: Blood Proteins; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cystadenocarcinoma, Serous; Drug Synergism; Female; Galectin 3; Galectins; Gene Expression Regulation, Neoplastic; Humans; Integrins; Neoplasm Grading; Ovarian Neoplasms; Paclitaxel; Pectins; Phosphorylation; Signal Transduction; Spheroids, Cellular; STAT3 Transcription Factor; Tumor Cells, Cultured

Galectin-3 (Gal-3) is a carbohydrate-binding protein which is thought to be involved in cancer progression but its contribution to epithelial ovarian cancer (EOC) remains unclear. The present study sought to determine the role of Gal-3 in chemoresistance of the human SKOV-3 ovarian cancer cell line to paclitaxel (PTX) using recombinant human Gal-3 (rhGal-3) and PectaSol-C modified citrus pectin (Pect-MCP) as a specific Gal-3 competitive inhibitor. Our results showed 41% increased cell proliferation, 36% decreased caspase-3 activity and 33.6% increased substrate-dependent adhesion in the presence of rhGal-3 compared to the control case (p<0.001). Treatment of cells with a non-effective dose of PTX (100nM) and 0.1% Pect-MCP in combination revealed synergistic cytotoxic effects with 75% reduced cell viability and subsequent 3.9-fold increase in caspase-3 activity. Moreover, there was 39% decrease in substrate-dependent adhesion compared to control (p<0.001). These results suggest that inhibition of Gal-3 could be a useful therapeutic tool for combination therapy of ovarian cancer.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Blood Proteins; Blotting, Western; Cell Adhesion; Cell Cycle; Cell Movement; Cell Proliferation; Citrus; Drug Synergism; Female; Galectin 3; Galectins; Humans; Ovarian Neoplasms; Paclitaxel; Pectins; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured; Umbilical Cord

Ovarian cancer is the ninth most common cancer amongst women and ranked as fifth in terms of the cause of cancer related mortality accounting for more deaths than any other cancer of the female reproductive system. Gemcitabine is the most common chemotherapeutic agent used in the treatment of ovarian cancer despite of its disadvantage of having a very lesser half life. In this study, we have envisaged the use of a highly porous, biomimetic and implantable pectin scaffold embedded with gemcitabine loaded fibrin nanoconstructs to improve the half life of the drug, thereby providing localized therapy for ovarian cancer. The controlled and sustained release of the chemokine from the scaffold system was extensively analyzed in vitro different pH environments. The composite scaffolds were found to be highly biocompatible when tested with mammalian cell lines. The excellent cytotoxicity and apoptosis responses induced in ovarian cancer, PA- 1 cell lines proved that the nanocomposite Pectin scaffolds loaded with specific chemokine can be used as implantable "therapeutic wafers" for distracting metastatic cancer cells and thus improve the survival rate of ovarian cancer afflicted individuals.

Topics: Antimetabolites, Antineoplastic; Cell Adhesion; Cell Line, Tumor; Cell Survival; Chitosan; Deoxycytidine; Drug Delivery Systems; Female; Fibrin; Gemcitabine; Humans; Nanocomposites; Ovarian Neoplasms; Pectins; Porosity; Tissue Scaffolds