Dataset Information

Heterogeneous Responses of Ovarian Cancer Cells to Silver Nanoparticles as a Single Agent and in Combination with Cisplatin.

ABSTRACT: We investigated the effects of silver nanoparticle (AgNP) exposure in three ovarian cancer cell lines (A2780, SKOV3, and OVCAR3). We found that AgNPs were highly cytotoxic toward A2780 and SKOV3 cells but OVCAR3 cells were less sensitive to AgNPs. In agreement with the cytotoxicity data, AgNPs caused DNA damage in A2780 and SKOV3 cells, but not in OVCAR3 cells. A2780 and SKOV3 showed higher levels of basal reactive oxygen species (ROS) relative to OVCAR3 cells. AgNP exposure increased ROS levels in both A2780 and SKOV3 cells, but not in OVCAR3 cells. We found that the heterogeneous cytotoxicity was specific to the uptake of intact particles and was not due to differences in sensitivity to silver ions. Furthermore, the combination of AgNPs and standard-of-care platinum therapy, cisplatin (cis-diamminedichloroplatinum(II), CDDP), was synergistic for treatment of A2780 andOVCAR3 cells and the combination of AgNPs and CDDP showed a favorable dose reduction in all cell lines tested. These results provide insight into potential applications of AgNPs for treatment of ovarian cancer.

SUBMITTER: Fahrenholtz CD

PROVIDER: S-EPMC6052800 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Heterogeneous Responses of Ovarian Cancer Cells to Silver Nanoparticles as a Single Agent and in Combination with Cisplatin.

Fahrenholtz Cale D CD Swanner Jessica J Ramirez-Perez Maria M Singh Ravi N RN

Journal of nanomaterials 20170426

We investigated the effects of silver nanoparticle (AgNP) exposure in three ovarian cancer cell lines (A2780, SKOV3, and OVCAR3). We found that AgNPs were highly cytotoxic toward A2780 and SKOV3 cells but OVCAR3 cells were less sensitive to AgNPs. In agreement with the cytotoxicity data, AgNPs caused DNA damage in A2780 and SKOV3 cells, but not in OVCAR3 cells. A2780 and SKOV3 showed higher levels of basal reactive oxygen species (ROS) relative to OVCAR3 cells. AgNP exposure increased ROS levels ...[more]

PMID: 30034459

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Project description:Extracellular vesicles (EVs) are on the edge of innovation aimed at regenerative and therapeutic applications, including wound healing, by containing therapeutic agents originating from secreting cells. Moreover, silver nanoparticles (AgNPs) play a role in wound healing because they have antiseptic activities. Therefore, in this study, we used sequencing technology to investigate the mRNA profile in UCMSC-derived exosomes (EXs). We also attempted to determine the role of the transcriptome, particularly in cutaneous wound healing, using bioinformatics analysis. Additionally, we investigated the efficacy of utilising a combination of UCMSC-derived EXs and AgNPs on burned animal models. Results showed that a large number of protein-coding genes (4578 genes) have been detected in UCMSC-derived EXs, among which 2004 genes are upregulated in exosomes while 2574 genes are downregulated compared to secreting cells. Interestingly, many genes enriched in exosomes were associated with the biology of the wound healing process. Gene ontology (GO) term and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis indicated the upregulated exosomal genes belonging to GO terms and KEGG pathways related to signaling pathways such as DNA replication, ribosome, cell cycle, and pyrimidine metabolism. Further investigations that aimed to test exosomes and AgNPs in wound healing stimulation confirmed the faster healing capacity belongs to all exosomes, AgNPs, and a combination of EXs and AgNPs in the early healing process. The exosomes also expressed their capacity to enhance the dermal fibroblast proliferation. Our findings indicated the selective sorting of mRNAs into EXs, the potential of EXs, and the combination of EXs with AgNPs in cutaneous wound healing. Extracellular vesicles (EVs) are on the edge of innovation aimed at regenerative and therapeutic applications, including wound healing, by containing therapeutic agents originating from secreting cells. Moreover, silver nanoparticles (AgNPs) play a role in wound healing because they have antiseptic activities. Therefore, in this study, we used sequencing technology to investigate the mRNA profile in UCMSC-derived exosomes (EXs). We also attempted to determine the role of the transcriptome, particularly in cutaneous wound healing, using bioinformatics analysis. Additionally, we investigated the efficacy of utilising a combination of UCMSC-derived EXs and AgNPs on burned animal models. Results showed that a large number of protein-coding genes (4578 genes) have been detected in UCMSC-derived EXs, among which 2004 genes are upregulated in exosomes while 2574 genes are downregulated compared to secreting cells. Interestingly, many genes enriched in exosomes were associated with the biology of the wound healing process. Gene ontology (GO) term and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis indicated the upregulated exosomal genes belonging to GO terms and KEGG pathways related to signaling pathways such as DNA replication, ribosome, cell cycle, and pyrimidine metabolism. Further investigations that aimed to test exosomes and AgNPs in wound healing stimulation confirmed the faster healing capacity belongs to all exosomes, AgNPs, and a combination of EXs and AgNPs in the early healing process. The exosomes also expressed their capacity to enhance the dermal fibroblast proliferation. Our findings indicated the selective sorting of mRNAs into EXs, the potential of EXs, and the combination of EXs with AgNPs in cutaneous wound healing. Extracellular vesicles (EVs) are on the edge of innovation aimed at regenerative and therapeutic applications, including wound healing, by containing therapeutic agents originating from secreting cells. Moreover, silver nanoparticles (AgNPs) play a role in wound healing because they have antiseptic activities. Therefore, in this study, we used sequencing technology to investigate the mRNA profile in UCMSC-derived exosomes (EXs). We also attempted to determine the role of the transcriptome, particularly in cutaneous wound healing, using bioinformatics analysis. Additionally, we investigated the efficacy of utilising a combination of UCMSC-derived EXs and AgNPs on burned animal models. Results showed that a large number of protein-coding genes (4578 genes) have been detected in UCMSC-derived EXs, among which 2004 genes are upregulated in exosomes while 2574 genes are downregulated compared to secreting cells. 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Project description:BACKGROUND:Berberine (BBR), a compound extracted from a variety of medicinal herbs, has been shown multiple pharmacological effects against cancer cells of different origins. Cisplatin (DDP) is known as an effective chemotherapeutic agent against cancer by inducing DNA damage and cell apoptosis. However, the effect of the combined used of BBR and DDP on cell necroptosis in ovarian cancer has not been reported. METHODS:OVCAR3 and three patient-derived primary ovarian cancer cell lines (POCCLs) were chosen as the experimental objects. To determine the potential anti-cancer activity of BBR and DDP in combination, we firstly treated OVCAR3 and POCCLs cells with BBR and/or DDP. The cell viability of OVCAR3 and POCCLs with treatment of BBR or DDP for different hours was measured by CCK-8 assay. Flow cytometry was used to analyze cell cycle distribution and changes in apoptotic cells after treatment with BBR and/or DDP. The morphological changes of OVCAR3 cells were observed by using Transmission electron microscopy (TEM) analysis. Proliferation, apoptosis and necroptosis related markers of OVCAR3 and POCCLs with treatment of BBR or DDP were measured by RT-qPCR, western blotting and immunofluorescence assay. RESULTS:Our results demonstrated that BBR significantly inhibited the proliferation of OVCAR3 and primary ovarian cancer cells in a dose- and time-dependent manner. The combination treatment of BBR and DDP had a prominent inhibitory effect on cancer cell growth and induced G0/G1 cell cycle arrest. TEM revealed that the majority of cells after BBR or DDP treatment had an increasing tendency of typical apoptotic and necrotic cell death morphology. Besides, BBR and DDP inhibited the expression of PCNA and Ki67 and enhanced the expression and activation of Caspase-3, Caspase-8, RIPK3 and MLKL. CONCLUSION:This study proposed that the combination therapy of BBR and DDP markedly enhanced more ovarian cancer cell death by inducing apoptosis and necroptosis, which may improve the anticancer effect of chemotherapy drugs. The apoptosis involved the caspase-dependent pathway, while the necroptosis involved the activation of the RIPK3-MLKL pathway. We hope our findings might provide a new insight for the potential of BBR as a therapeutic agent in the treatment of ovarian cancer.

Dataset Information

Heterogeneous Responses of Ovarian Cancer Cells to Silver Nanoparticles as a Single Agent and in Combination with Cisplatin.

Publications

Heterogeneous Responses of Ovarian Cancer Cells to Silver Nanoparticles as a Single Agent and in Combination with Cisplatin.

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