In vitro and ex vivo vanadium antitumor activity in (TGF-beta)-induced EMT. Synergistic activity with carboplatin and correlation with tumor metastasis in cancer patients
2016 (English)In: International Journal of Biochemistry and Cell Biology, ISSN 1357-2725, E-ISSN 1878-5875, Vol. 74, 121-134 p.Article in journal (Refereed) PublishedText
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-beta (TGF-beta) 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-beta)-induced EMT remains unclear. In the present study, we report for the first time on the inhibitory effects of vanadium on (TGF-beta)-mediated EMT followed by down-regulation of ex vivo cancer stem cell markers. The results demonstrate blockage of (TGF-beta)-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 G(0)/G(1) 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.
Place, publisher, year, edition, pages
2016. Vol. 74, 121-134 p.
Vanadium, TGF-beta, Epithelial mesenchymal transition, Cancer stem cells, Antitumor activity synergism
Cancer and Oncology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
IdentifiersURN: urn:nbn:se:uu:diva-297333DOI: 10.1016/j.biocel.2016.02.015ISI: 000374807800011PubMedID: 26916505OAI: oai:DiVA.org:uu-297333DiVA: diva2:942201