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

• Published in: International journal of molecular sciences 2018-03, Vol.19 (3), p.710
• Main Authors: Choi, Yun-Jung, Gurunathan, Sangiliyandi, Kim, Jin-Hoi
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Biomarkers; Cancer therapies; Cell Line, Tumor; Cell Survival - drug effects; Chemotherapy; Cytotoxicity; Dose-Response Relationship, Drug; Female; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Graphene; Graphite - chemistry; Humans; Immunophenotyping; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Low concentrations; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Metal Nanoparticles - chemistry; Metal Nanoparticles - ultrastructure; Mitochondria; Models, Biological; Nanocomposites; Nanoparticles; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Ovarian cancer; Ovarian Neoplasms; Oxides - chemistry; Pyrans - chemistry; Pyrans - pharmacology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Salinomycin; Silver; Silver - chemistry; Stem cells; Tumor cells; Tumor Stem Cell Assay; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19030710

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.