PMID- 29494563 OWN - NLM STAT- MEDLINE DCOM- 20180827 LR - 20240314 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 19 IP - 3 DP - 2018 Mar 1 TI - Graphene Oxide-Silver Nanocomposite Enhances Cytotoxic and Apoptotic Potential of Salinomycin in Human Ovarian Cancer Stem Cells (OvCSCs): A Novel Approach for Cancer Therapy. LID - 10.3390/ijms19030710 [doi] LID - 710 AB - 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. FAU - Choi, Yun-Jung AU - Choi YJ AD - Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea. choi_yunjung@naver.com. FAU - Gurunathan, Sangiliyandi AU - Gurunathan S AD - Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea. sangiliyandi@konkuk.ac.kr. FAU - Kim, Jin-Hoi AU - Kim JH AUID- ORCID: 0000-0003-1232-5307 AD - Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea. jhkim541@konkuk.ac.kr. LA - eng PT - Journal Article DEP - 20180301 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antineoplastic Agents) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Biomarkers) RN - 0 (Oxides) RN - 0 (Pyrans) RN - 0 (Reactive Oxygen Species) RN - 3M4G523W1G (Silver) RN - 62UXS86T64 (salinomycin) RN - 7782-42-5 (Graphite) SB - IM MH - Antineoplastic Agents/chemistry/*pharmacology MH - Apoptosis/*drug effects MH - Apoptosis Regulatory Proteins/genetics/metabolism MH - Biomarkers MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Dose-Response Relationship, Drug MH - Female MH - Gene Expression Regulation, Neoplastic/drug effects MH - *Graphite/chemistry MH - Humans MH - Immunophenotyping MH - Membrane Potential, Mitochondrial/drug effects MH - *Metal Nanoparticles/chemistry/ultrastructure MH - Models, Biological MH - Neoplastic Stem Cells/*drug effects/metabolism MH - Ovarian Neoplasms MH - *Oxides/chemistry MH - Pyrans/chemistry/*pharmacology MH - Reactive Oxygen Species/metabolism MH - *Silver/chemistry MH - Tumor Stem Cell Assay PMC - PMC5877571 OTO - NOTNLM OT - apoptosis OT - cytotoxicity OT - human ovarian cancer cells OT - ovarian cancer stem cells (OvCSCs) OT - reduced graphene oxide-silver nanocomposite (rGO-Ag) COIS- The authors declare no conflict of interest. EDAT- 2018/03/02 06:00 MHDA- 2018/08/28 06:00 PMCR- 2018/03/01 CRDT- 2018/03/02 06:00 PHST- 2018/02/01 00:00 [received] PHST- 2018/02/22 00:00 [revised] PHST- 2018/02/26 00:00 [accepted] PHST- 2018/03/02 06:00 [entrez] PHST- 2018/03/02 06:00 [pubmed] PHST- 2018/08/28 06:00 [medline] PHST- 2018/03/01 00:00 [pmc-release] AID - ijms19030710 [pii] AID - ijms-19-00710 [pii] AID - 10.3390/ijms19030710 [doi] PST - epublish SO - Int J Mol Sci. 2018 Mar 1;19(3):710. doi: 10.3390/ijms19030710.