title: Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells.
abstract: 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.
authors.affiliation: Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. yunjungc@konkuk.ac.kr.
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. saladinhyun@naver.com.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. woong1211@naver.com.
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Han
authors.affiliation: Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. np-gennao@hanmail.net.
authors.forename: Eunsu
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. ohjw62@gmail.com.
authors.forename: Oh
authors.initials: O
authors.lastname: Jae-Wook
authors.affiliation: Swine Consulting Group, HanByol Farm Tech, Gyeonggi 463-785, Korea. kissleevet@gmail.com.
authors.forename: Seung Yoon
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. jhkim541@konkuk.ac.kr.
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea. sangiliyandi@konkuk.ac.kr.
authors.forename: Sangiliyandi
authors.initials: S
authors.lastname: Gurunathan
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D012834:Silver / Q000494:pharmacology*; D013997:Time Factors; D014410:Tumor Stem Cell Assay
chemical_list: D000071916:AC133 Antigen; D012834:Silver; D000444:Aldehyde Dehydrogenase
keywords: cancer therapy; cell viability; cytotoxicity; ovarian cancer cells; ovarian cancer stem cells; silver nanoparticles