PMID- 27973444 OWN - NLM STAT- MEDLINE DCOM- 20170403 LR - 20240326 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 17 IP - 12 DP - 2016 Dec 12 TI - Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells. LID - 2077 AB - The cancer stem cell (CSC) hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs) have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs). In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells) and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH) and CD133 by fluorescence-activated cell sorting (FACS). The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and mitochondrial membrane potential (mt-MP). The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1-2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells) and ALDH(+)/CD133(+) colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH(+)/CD133(+) subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells). These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH(+)/CD133(+) subpopulation of cells. FAU - Choi, Yun-Jung AU - Choi YJ AD - Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. yunjungc@konkuk.ac.kr. FAU - Park, Jung-Hyun AU - Park JH AD - Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. saladinhyun@naver.com. FAU - Han, Jae Woong AU - Han JW AD - Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. woong1211@naver.com. FAU - Kim, Eunsu AU - Kim E AD - Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. np-gennao@hanmail.net. FAU - Jae-Wook, Oh AU - Jae-Wook O AD - Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. ohjw62@gmail.com. FAU - Lee, Seung Yoon AU - Lee SY AD - Swine Consulting Group, HanByol Farm Tech, Gyeonggi 463-785, Korea. kissleevet@gmail.com. FAU - Kim, Jin-Hoi AU - Kim JH AD - Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. jhkim541@konkuk.ac.kr. FAU - Gurunathan, Sangiliyandi AU - Gurunathan S AD - Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. sangiliyandi@konkuk.ac.kr. LA - eng PT - Journal Article DEP - 20161212 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (AC133 Antigen) RN - 3M4G523W1G (Silver) RN - EC 1.2.1.3 (Aldehyde Dehydrogenase) SB - IM MH - AC133 Antigen/metabolism MH - Aldehyde Dehydrogenase/metabolism MH - Cell Death/drug effects MH - Cell Line, Tumor MH - Cell Separation MH - Cell Survival/drug effects MH - Female MH - Humans MH - Metal Nanoparticles/*chemistry MH - Neoplastic Stem Cells/drug effects/*pathology MH - Ovarian Neoplasms/*pathology MH - Silver/*pharmacology MH - Time Factors MH - Tumor Stem Cell Assay PMC - PMC5187877 OTO - NOTNLM OT - cancer therapy OT - cell viability OT - cytotoxicity OT - ovarian cancer cells OT - ovarian cancer stem cells OT - silver nanoparticles COIS- The authors declare no conflict of interest. EDAT- 2016/12/16 06:00 MHDA- 2017/04/04 06:00 PMCR- 2016/12/01 CRDT- 2016/12/16 06:00 PHST- 2016/09/09 00:00 [received] PHST- 2016/11/17 00:00 [revised] PHST- 2016/11/30 00:00 [accepted] PHST- 2016/12/16 06:00 [entrez] PHST- 2016/12/16 06:00 [pubmed] PHST- 2017/04/04 06:00 [medline] PHST- 2016/12/01 00:00 [pmc-release] AID - ijms17122077 [pii] AID - ijms-17-02077 [pii] AID - 10.3390/ijms17122077 [doi] PST - epublish SO - Int J Mol Sci. 2016 Dec 12;17(12):2077. doi: 10.3390/ijms17122077.