title: In vitro and ex vivo vanadium antitumor activity in (TGF-β)-induced EMT. Synergistic activity with carboplatin and correlation with tumor metastasis in cancer patients.
abstract: Epithelial to mesenchymal transition (EMT) plays a key role in tumor progression and metastasis as a crucial event for cancer cells to trigger the metastatic niche. Transforming growth factor-β (TGF-β) has been shown to play an important role as an EMT inducer in various stages of carcinogenesis. Previous reports had shown that antitumor vanadium inhibits the metastatic potential of tumor cells by reducing MMP-2 expression and inducing ROS-dependent apoptosis. However, the role of vanadium in (TGF-β)-induced EMT remains unclear. In the present study, we report for the first time on the inhibitory effects of vanadium on (TGF-β)-mediated EMT followed by down-regulation of ex vivo cancer stem cell markers. The results demonstrate blockage of (TGF-β)-mediated EMT by vanadium and reduction in the mitochondrial potential of tumor cells linked to EMT and cancer metabolism. Furthermore, combination of vanadium and carboplatin (a) resulted in synergistic antitumor activity in ex vivo cell cultures, and (b) prompted G0/G1 cell cycle arrest and sensitization of tumor cells to carboplatin-induced apoptosis. Overall, the findings highlight the multifaceted antitumor action of vanadium and its synergistic antitumor efficacy with current chemotherapy drugs, knowledge that could be valuable for targeting cancer cell metabolism and cancer stem cell-mediated metastasis in aggressive chemoresistant tumors.
authors.affiliation: Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. Electronic address: spetanid@auth.gr.
authors.forename: Savvas
authors.initials: S
authors.lastname: Petanidis
authors.affiliation: Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. Electronic address: efi.kioseoglou@auth.gr.
authors.forename: Efrosini
authors.initials: E
authors.lastname: Kioseoglou
authors.affiliation: Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece. Electronic address: kellybio4@hotmail.com.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Domvri
authors.affiliation: Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece. Electronic address: pzarog@hotmail.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Zarogoulidis
authors.affiliation: Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Uppsala SE-75124, Sweden. Electronic address: jon.carthy@licr.uu.se.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Carthy
authors.affiliation: Laboratory of Forensic Medicine and Toxicology, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece; Laboratory of General Biology, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. Electronic address: anestaki@auth.gr.
authors.forename: Doxakis
authors.initials: D
authors.lastname: Anestakis
authors.affiliation: Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Uppsala SE-75124, Sweden; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala SE-75123, Sweden. Electronic address: aris.moustakas@imbim.uu.se.
authors.forename: Aristidis
authors.initials: A
authors.lastname: Moustakas
authors.affiliation: Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. Electronic address: salif@auth.gr.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Salifoglou
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D015394:Molecular Structure; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014639:Vanadium / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D016212:Transforming Growth Factor beta; D014639:Vanadium; D016190:Carboplatin
keywords: Antitumor activity synergism; Cancer stem cells; Epithelial mesenchymal transition; TGF-β; Vanadium