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Int. J. Mol. Sci. 2018, 19(3), 710; https://doi.org/10.3390/ijms19030710

Graphene Oxide–Silver Nanocomposite Enhances Cytotoxic and Apoptotic Potential of Salinomycin in Human Ovarian Cancer Stem Cells (OvCSCs): A Novel Approach for Cancer Therapy

Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea
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Received: 1 February 2018 / Revised: 22 February 2018 / Accepted: 26 February 2018 / Published: 1 March 2018
(This article belongs to the Section Molecular Toxicology)
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Abstract

The use of graphene to target and eliminate cancer stem cells (CSCs) is an alternative approach to conventional chemotherapy. We show the biomolecule-mediated synthesis of reduced graphene oxide–silver nanoparticle nanocomposites (rGO–Ag) using R-phycoerythrin (RPE); the resulting RPE–rGO–Ag was evaluated in human ovarian cancer cells and ovarian cancer stem cells (OvCSCs). The synthesized RPE–rGO–Ag nanocomposite (referred to as rGO–Ag) was characterized using various analytical techniques. rGO–Ag showed significant toxicity towards both ovarian cancer cells and OvCSCs. After 3 weeks of incubating OvCSCs with rGO–Ag, the number of A2780 and ALDH+CD133+ colonies was significantly reduced. rGO–Ag was toxic to OvCSCs and reduced cell viability by mediating the generation of reactive oxygen species, leakage of lactate dehydrogenase, reduced mitochondrial membrane potential, and enhanced expression of apoptotic genes, leading to mitochondrial dysfunction and possibly triggering apoptosis. rGO–Ag showed significant cytotoxic potential towards highly tumorigenic ALDH+CD133+ cells. The combination of rGO–Ag and salinomycin induced 5-fold higher levels of apoptosis than each treatment alone. A combination of rGO–Ag and salinomycin at very low concentrations may be suitable for selectively killing OvCSCs and sensitizing tumor cells. rGO–Ag may be a novel nano-therapeutic molecule for specific targeting of highly tumorigenic ALDH+CD133+ cells and eliminating CSCs. This study highlights the potential for targeted therapy of tumor-initiating cells. View Full-Text
Keywords: reduced graphene oxide–silver nanocomposite (rGO–Ag); human ovarian cancer cells; ovarian cancer stem cells (OvCSCs); cytotoxicity; apoptosis reduced graphene oxide–silver nanocomposite (rGO–Ag); human ovarian cancer cells; ovarian cancer stem cells (OvCSCs); cytotoxicity; apoptosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Choi, Y.-J.; Gurunathan, S.; Kim, J.-H. Graphene Oxide–Silver Nanocomposite Enhances Cytotoxic and Apoptotic Potential of Salinomycin in Human Ovarian Cancer Stem Cells (OvCSCs): A Novel Approach for Cancer Therapy. Int. J. Mol. Sci. 2018, 19, 710.

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