Repository of Research and Investigative Information

Repository of Research and Investigative Information

دانشگاه علوم پزشکی و خدمات بهداشتی درمانی زنجان

Enhanced penetration and cytotoxicity of metformin and collagenase conjugated gold nanoparticles in breast cancer spheroids

(2019) Enhanced penetration and cytotoxicity of metformin and collagenase conjugated gold nanoparticles in breast cancer spheroids. Life Sci. p. 116545. ISSN 0024-3205

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AIMS: The extracellular matrix (ECM) within the tumor nest plays a key role in cancer cell proliferation and invasion. It has been proven that the increased density of ECM, especially collagen network, correlates with the poor distribution of gold-nanoparticles (GNPs) to the tumor mass. Here, for the first time, we examined the combined effect of collagenase (COL) with metformin (MET)-conjugated GNPs on mammosphere generated from JIMT-1 breast cell line in vitro. MAIN METHODS: Mammospheres (on days 7 and 14) and monolayer culture were treated with MET, MET-GNPs, and a mixture of COL-GNPs and MET-GNPs for 5days. To assess the impacts of the engineered nanoparticles (NPs) on the survival/apoptosis of cancer cells and cancer stem cells (CSCs), the amount/activity of collagen and the expression of pyruvate kinase M2, different methods were applied, including MTT, flow cytometry, immunofluorescence, ELISA and real-time PCR analyses. Our results confirmed the enhanced cytotoxic effects of MET-GNPs combined with COL-GNPs on mammospheres compared to the cells treated with MET alone or MET-GNPs. KEY FINDINGS: Upon treatment with the mixture of MET-GNPs and COL-GNPs, the population of the apoptotic cells was significantly increased. A marked reduction was found in the number of CD24(-)/CD44(+) CSCs and the amount of collagen in the group received a mixture of MET-GNPs and COL-GNPs. SIGNIFICANCE: Based on our findings, the use of COL can improve the cellular interaction/penetration of MET-GNPs in mammospheres and its antitumor impacts on the CSCs.

Item Type: Article
Keywords: Apoptosis/drug effects,Breast Neoplasms/*drug therapy/metabolism/pathology,Cancer stem cells,Cell Line, Tumor,Cell Proliferation/drug effects,Cell Survival/drug effects,Collagenase,Collagenases/*administration & dosage/pharmacokinetics/pharmacology,Extracellular Matrix/drug effects,Female,Gold nanoparticles,Humans,Mammospheres,Metal Nanoparticles/*administration & dosage,Metformin,Metformin/*administration & dosage/pharmacokinetics,Nanomedicine,Neoplasm Invasiveness,Neoplastic Stem Cells/drug effects/metabolism,Spheroids, Cellular/drug effects/metabolism
Subjects: QU Biochemistry. Cell Biology and Genetics > QU 300-560 Cell Biology and Genetics
QZ Pathology > QZ 200-380 Neoplasms
Page Range: p. 116545
Journal or Publication Title: Life Sci
Abstract and Indexing: ISI, Pubmed, Scopus
Quartile : Q2
Volume: 231
Publisher: Elsevier
Identification Number:
ISSN: 0024-3205
ISBN: 0024-3205
Depositing User: خانم فائزه مظفری

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