title: Classical and atypical resistance of cancer cells as a target for resveratrol.
abstract: The phenomenon of cancer cell resistance to chemotherapeutics is the main cause of insensitivity to anticancer therapy. Thus, the current challenge remains searching for substances sensitising the activity of cytostatic drugs. In this respect, resveratrol is a very promising therapeutic agent. It has pleiotropic effect on cancer cells, which can play a key role in numerous resistance mechanisms, both classical and atypical. The purpose of the present study was to assess the effect of resveratrol on the inhibition of human pancreatic cancer cell proliferation and on the level of cytostatic resistance-associated proteins. The study was performed on human pancreatic cancer cell lines EPP85-181P (control), EPP85-181RDB (daunorubicin resistance) and EPP85-181PRNOV (mitoxantrone resistance). The effect of resveratrol on the viability and proliferation of the studied cell lines was evaluated by SRB assay, whereas cell cycle arrest and cytostatic accumulation by FACS. Western blot analysis was used to determine the level of P-glycoprotein, topoisomerase II α and β and immunofluorescence technique to visualise the proteins in the cells. Resveratrol inhibited proliferation of all studied cell lines. Phase-specific cell cycle arrest depended on the type of cancer cells. Resveratrol decreased the level and activity of P-gp in EPP85-181RDB cells. In EPP85-181PRNOV cells, expression of both TopoII isoforms increased in a statistically significant manner. The results of in vitro studies support the possibility of potential use of resveratrol in breaking cancer cell resistance to chemotherapeutic drugs.
authors.affiliation: Department of Histology and Embryology, Medical University, 50-368 Wroclaw, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Borska
authors.affiliation: Department of Histology and Embryology, Medical University, 50-368 Wroclaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Pedziwiatr
authors.affiliation: Department of Histology and Embryology, Medical University, 50-368 Wroclaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Danielewicz
authors.affiliation: Department of Histology and Embryology, Medical University, 50-368 Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Nowinska
authors.affiliation: Department of Histology and Embryology, Medical University, 50-368 Wroclaw, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Pula
authors.affiliation: Department of Histology and Embryology, Medical University, 50-368 Wroclaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Drag-Zalesinska
authors.affiliation: Department of Histology and Embryology, Medical University, 50-368 Wroclaw, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Olbromski
authors.affiliation: Department of Histology and Embryology, Medical University, 50-368 Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gomulkiewicz
authors.affiliation: Department of Histology and Embryology, Medical University, 50-368 Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Dziegiel
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D000077185:Resveratrol