Microcystin LR Shows Cytotoxic Activity Against Pancreatic Cancer Cells Expressing the Membrane OATP1B1 and OATP1B3 Transporters.
| Τίτλος | Microcystin LR Shows Cytotoxic Activity Against Pancreatic Cancer Cells Expressing the Membrane OATP1B1 and OATP1B3 Transporters. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Kounnis, V., Chondrogiannis G., Mantzaris M. D., Tzakos A. G., Fokas D., Papanikolaou N. A., Galani V., Sainis I., & Briasoulis E. |
| Journal | Anticancer Res |
| Volume | 35 |
| Issue | 11 |
| Pagination | 5857-65 |
| Date Published | 2015 Nov |
| ISSN | 1791-7530 |
| Λέξεις κλειδιά | Amino Acid Sequence, Apoptosis, Biological Transport, Blotting, Western, Cell Proliferation, Enzyme Inhibitors, Flow Cytometry, Humans, Immunoenzyme Techniques, Microcystins, Molecular Docking Simulation, Molecular Sequence Data, Organic Anion Transporters, Organic Anion Transporters, Sodium-Independent, Pancreatic Neoplasms, Phosphoprotein Phosphatases, Protein Conformation, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Sequence Homology, Amino Acid, Tumor Cells, Cultured |
| Abstract | Microcystin-LR (MC-LR) is a cyanobacterial cyclopeptide, known for its unique ability to cause acute liver injury. Its cellular uptake is facilitated by specific transmembrane organic anion-transporting polypeptides (OATPs) specifically OATP1B1 and 1B3. The objective of the present study was to investigate the expression of OATPs 1A2, 1B1 and 1B3 in pancreatic cancer cell lines BxPC-3 and MIA PACA-2 and assess their role in MC-LR-mediated cytotoxicity by using the novel xCELLigence system and flow cytometry. OATP1B1 and 1B3 were found to be expressed in both cell lines at both the mRNA and protein levels. The cytotoxic effects of MC-LR were proportionally related to the expression of these transporters. Moreover the cytotoxic potency of MC-LR was found superior to gemcitabine. Based on the expression of the organic anion transporting polypeptides 1B1 and 1B3 in pancreatic carcinoma tissue and cell lines and the potent cytotoxicity induced by MC-LR in vitro, we propose that this molecule could be held as structural basis for the development of novel targeted-compounds against pancreatic cancer. |
| Alternate Journal | Anticancer Res. |
| PubMed ID | 26504008 |
