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International Journal of Nanomedicine 2018Nanotechnology has gained important interest, especially in the development of new therapies; the application of gold nanoparticles (AuNPs) in the treatment and...
BACKGROUND
Nanotechnology has gained important interest, especially in the development of new therapies; the application of gold nanoparticles (AuNPs) in the treatment and detection of diseases is a growing trend in this field. As cancer represents a serious health problem around the world, AuNPs are studied as potential drugs or drug carriers for anticancer agents. Recent studies show that AuNPs stabilized with chitosan (CH) possess interesting biological activities, including potential antitumor effects that could be selective to cancer cells.
MATERIALS AND METHODS
In this study, we synthesized sodium citrate-AuNPs and CH-capped AuNPs of 3-10 nm, and analyzed their cytotoxicity in cervical (HeLa) and breast (MCF-7) cancer cells, and in peripheral blood mononuclear cells (PBMCs). Then, we evaluated the clonogenic potential, cell cycle, nuclear alterations, caspase dependence, and reactive oxygen species (ROS) production in HeLa and MCF-7 cells after chitosan gold nanoparticles (CH-AuNPs) exposure.
RESULTS
Our data showed that CH-AuNPs are cytotoxic in a dose-dependent manner in the cancer cell lines tested, while they induce low cytotoxicity in PBMCs. Sodium citrate gold nanoparticles did not show cytotoxic effects. In both HeLa and MCF-7 cell lines, CH-AuNPs inhibit clonogenic potential without inducing cell cycle arrest or nuclear alterations. The cell death mechanism is specific for the type of cancer cell line tested, as it depends on caspase activation in HeLa cells, whereas it is caspase independent in MCF-7 cells. In all cases, ROS production is mandatory for cell death induction by CH-AuNPs, as ROS inhibition with N-acetyl cysteine inhibits cell death.
CONCLUSION
Our results show that CH-AuNPs are selective for HeLa and MCF-7 cancer cells, rather than normal PBMCs, and that ROS production seems to be a conserved feature of the cell death mechanism induced by CH-AuNPs. These results improve the knowledge of CH-AuNPs and open the way to the design of new pharmacological strategies using these agents against cancer.
Topics: Antineoplastic Agents; Caspases; Cell Cycle Checkpoints; Cell Death; Cell Survival; Chitosan; Dose-Response Relationship, Drug; Female; Gold; HeLa Cells; Humans; Leukocytes, Mononuclear; MCF-7 Cells; Metal Nanoparticles; Reactive Oxygen Species
PubMed: 29910612
DOI: 10.2147/IJN.S165289 -
Nanoscale Apr 2024Anisotropic gold (Au) nanostructures have been widely explored for various nanomedicine applications. While these nanomaterials have shown great promise for disease...
Anisotropic gold (Au) nanostructures have been widely explored for various nanomedicine applications. While these nanomaterials have shown great promise for disease theranostics, particularly for cancer diagnosis and treatment, the utilization and clinical translation of anisotropic Au nanostructures have been limited by their high phagocytic uptake and clearance and low cancer targeting specificity. Numerous efforts have thus been made toward mitigating these challenges. Many conventional strategies, however, rely on all-synthetic materials, involve complex chemical processes, or have low product throughput and reproducibility. Herein, by integrating cell membrane coating and microfluidic technologies, a high-throughput bioinspired approach for synthesizing biomimetic anisotropic Au nanostructures with minimized phagocytic uptake and improved cancer cell targeting is reported. Through continuous hydrodynamic flow focusing, mixing, and sonication, Au nanostructures are encapsulated within the macrophage and cancer cell membrane vesicles effectively. The fabricated nanostructures are uniform and highly stable in serum. Importantly, the macrophage membrane vesicle-encapsulated Au nanostructures can be preferentially internalized by breast cancer cells, but not by macrophages. Overall, this study has demonstrated the feasibility of employing an integrated microfluidic-sonication technique to formulate uniform and highly stable biomimetic anisotropic nanostructures for enhanced cancer theranostic applications.
Topics: Gold; Humans; Anisotropy; Cell Membrane; Animals; Mice; Macrophages; Metal Nanoparticles; RAW 264.7 Cells; Cell Line, Tumor; Nanostructures; MCF-7 Cells
PubMed: 38563323
DOI: 10.1039/d4nr00415a -
Chemistry & Biodiversity Jan 2023Breast cancer is known as the most common type of invasive cancer in women. It is well-known that phenolic compounds play an important role in the treatment of this...
Breast cancer is known as the most common type of invasive cancer in women. It is well-known that phenolic compounds play an important role in the treatment of this disease. This study hypothesized that isoeugenol based two polyphenolic compounds 1 and 2 exerts its anti-proliferative effects through the induction of apoptosis and cell migration arrest on human breast cancer cell. Based on this hypothesis, the study aimed to investigate the anti-proliferative, anti-migrative effects of these compounds and their possible basic molecular mechanisms of action in MCF-7 cell lines. As a result, isoeugenol-based compounds 1 and 2 showed anti-proliferative, anti-apoptotic and anti-migrative effects in MCF-7 breast cancer cells. This result was supported by molecular analyzes and it was determined that there were changes in the expression of some gene regions involved in apoptosis and migration. Additionally, it was a remarkable result that cell viability inhibition did not occur in healthy breast tissue cells and no cytotoxic effect was observed. The existence of such a differentiation between cancer cells and healthy cells significantly increases the potential of these compounds to be used as chemotherapeutic drug active ingredients without side effects.
Topics: Humans; Female; MCF-7 Cells; Breast Neoplasms; Cell Proliferation; Polyphenols; Early Detection of Cancer; Antineoplastic Agents; Apoptosis; Cell Line, Tumor
PubMed: 36594615
DOI: 10.1002/cbdv.202200872 -
Advanced Healthcare Materials Aug 2023Dynamic interaction of cancer, immune, and stromal cells with extracellular matrix components modulates and resists the response of standard care therapies. To mimic...
Dynamic interaction of cancer, immune, and stromal cells with extracellular matrix components modulates and resists the response of standard care therapies. To mimic this, an in vitro 3D spheroid model is designed using liquid overlay method to simulate hot (MDA-MB-231) and cold (MCF-7) breast tumor microenvironment (TME). This study shows increased mesenchymal phenotype, stemness, and suppressive microenvironment in MDA-MB-231-spheroids upon exposure to doxorubicin. Intriguingly, the presence of human dermal fibroblasts enhances cancer-associated fibroblast phenotype in MDA-MB-231-spheroids through increased expression of CXCL12 and FSP-1, leading to higher infiltration of immune cells (THP-1 monocytes). However, a suppressive TME is observed in both subtypes, as seen by upregulation of M2-macrophage-specific CD68 and CD206 markers. Specifically, increased PDL-1 expressing tumor-associated macrophages along with FoxP3 expressing T regulatory cells are found in MDA-MB-231-spheroids when cultured with peripheral blood mononuclear cells. Further, it is found that the addition of 1-methyl-tryptophan, a potent indoleamine-2,3-dioxygenase-1 inhibitor, subsides the suppressive phenotype by decreasing the M2 polarization via downregulation of tryptophan metabolism and IL10 expression, particularly in MCF-7 triculture spheroids. Thus, the in vitro 3D spheroid model of TME can be utilized in therapeutics to validate immunomodulatory drugs for various breast cancer subtypes.
Topics: Humans; Female; Breast Neoplasms; Tumor Microenvironment; Leukocytes, Mononuclear; Tryptophan; Cell Line, Tumor; Spheroids, Cellular
PubMed: 37141121
DOI: 10.1002/adhm.202300164 -
Molecular Biology Reports Aug 2020Centaurea bruguierana, of the Asteraceae family, has a long history of use in traditional medicines for the treatment of various ailments. However, the anticancer...
Centaurea bruguierana, of the Asteraceae family, has a long history of use in traditional medicines for the treatment of various ailments. However, the anticancer activity and underlying mechanisms have not yet been assessed. The C. bruguierana was extracted with methanol and fractionated into four different fractions. Different cancer cells and one non-cancerous were used to examine the cytotoxic effects of these fractions using MTT assay. The most potent fraction, C. bruguierana ethyl acetate fraction (CB EtOAc), was explored for its effects on cell cycle progression and apoptosis induction by Hoechst staining and annexin V-PI double staining in MCF-7 cells. The expression of apoptosis-related genes was quantified by RT-PCR. Of all fractions, CB EtOAc was found to have the strongest antiproliferative activity (IC = 10 μg/mL) against MCF-7 cells. The antiproliferative activity of the CB EtOAc fraction against MCF-7 was correlated with arrested of cell cycle in the G1 phase, nuclear fragmentation, and the exposure of phosphatidylserine. The induction of apoptosis by CB EtOAc in MCF-7 cells was also associated with an increase in the Bax/Bcl-2 ratio and higher expression of caspases. Overall, our results demonstrated that CB EtOAc showed apoptosis-inducing effects, suggesting that C. bruguierana may be a promising source for a novel chemotherapeutic agents for the treatment of breast cancer.
Topics: 1-Butanol; A549 Cells; Acetates; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Breast Neoplasms; Cell Cycle Checkpoints; Cell Division; Cell Nucleus; Centaurea; Chloroform; Drug Screening Assays, Antitumor; Female; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Human Umbilical Vein Endothelial Cells; Humans; Inhibitory Concentration 50; MCF-7 Cells; Methanol; Neoplasm Proteins; Plant Components, Aerial; Plant Extracts; Solvents
PubMed: 32700127
DOI: 10.1007/s11033-020-05679-x -
PloS One 2022Perioperative blood transfusion in colorectal and some other cancer patients has been linked to the increased risk for recurrence, but a causal mechanism remains...
Responses of human colon and breast adenocarcinoma cell lines (LoVo, MCF7) and non-tumorigenic mammary epithelial cells (MCF-10A) to the acellular fraction of packed red blood cells in the presence and absence of cisplatin.
Perioperative blood transfusion in colorectal and some other cancer patients has been linked to the increased risk for recurrence, but a causal mechanism remains unclear. During the preparation and storage of packed red blood cells (PRBCs) bio-active substances accumulate in the acellular fraction (supernatant). Viability, proliferation, reactive oxygen species (ROS) levels, and DNA damage of colon (LoVo) and breast (MCF7) adenocarcinoma cells and non-tumorigenic MCF-10A cell line were determined in response to the supernatants of fresh and long-stored (day 42) PRBCs, leukoreduced (LR) or non-leukoreduced (NLR). The effect of supernatants on the cytotoxicity of cisplatin (cisPt) towards the cells was also examined. Supernatants, especially from a day 1 PRBCs, both LR and NLR, reduced the viability and inhibited proliferation of tumor cells (LoVo, MCF7), accompanying by the excessive ROS production, but these were not the case in MCF-10A. Moreover, supernatants had no effect on the cytotoxicity of cisPt against LoVo and MCF7 cells, while caused increased drug resistance in MCF-10A cells. The findings suggest the acellular fraction of PRBCs does not exhibit any pro-proliferative activity in the cancer cell lines studied. However, these are pioneering issues and require further research.
Topics: Adenocarcinoma; Breast Neoplasms; Cisplatin; Colon; Epithelial Cells; Erythrocytes; Female; Humans; MCF-7 Cells; Reactive Oxygen Species
PubMed: 35802725
DOI: 10.1371/journal.pone.0271193 -
Breast (Edinburgh, Scotland) Jun 2023Since patients with triple-negative breast cancer do not respond to hormone therapy, the main treatment method is the combination of chemotherapy and radiotherapy....
Since patients with triple-negative breast cancer do not respond to hormone therapy, the main treatment method is the combination of chemotherapy and radiotherapy. Because the DNA of the tumor cell is the target in both some chemotherapeutics and radiotherapy, problems may occur in individuals with a high DNA repair pathway. It is suggested that high expression of the Tip60 gene, which has an important role in repairing DNA damage, will increase the repair of DNA double-strand breaks in tumor cells, especially during radiotherapy treatment, thus reducing the response to treatment and adversely affecting treatment. In this study, for the first time, the role of the silenced and active Tip60 gene in response to radiotherapy in MDA-MB-231 and MCF-7 cells was investigated. For this purpose, the Tip60 gene was silenced by applying siRNA to the cell lines and UV was applied. In the study, cytotoxicity and DNA breaks were measured by MTT and COMET methods, and mRNA and protein expression values were measured by PCR and Raman spectrophotometer in silenced, unsilenced, UV-treated, and non-UV-treated cell lines. According to the results of the study, increased DNA damage was observed in MCF-7 cell lines in which the Tip60 gene was silenced, and radiotherapy was applied, compared to the cell lines with the Tip60 gene active. It was observed that DNA damage in MDA-MB-231 cell lines was less than in cell lines with the active Tip60 gene.
Topics: Humans; Female; Cell Line, Tumor; Breast Neoplasms; DNA Damage; MCF-7 Cells; DNA; Triple Negative Breast Neoplasms
PubMed: 37069013
DOI: 10.1016/j.breast.2023.04.001 -
Molecules (Basel, Switzerland) Nov 2017Tripentones represent an interesting class of compounds due to their significant cytotoxicity against different human tumor cells in the submicro-nanomolar range. New...
Tripentones represent an interesting class of compounds due to their significant cytotoxicity against different human tumor cells in the submicro-nanomolar range. New tripentone analogs, in which a pyridine moiety replaces the thiophene ring originating the fused azaindole system endowed with anticancer activity viz 8-thieno[2,3-]pyrrolizinones, were efficiently synthesized in four steps with fair overall yields (34-57%). All tripentone derivatives were tested in the range of 0.1-100 μM for cytotoxicity against two human tumor cell lines, HCT-116 (human colorectal carcinoma) and MCF-7 (human breast cancer). The most active derivative, with GI values of 4.25 µM and 20.73 µM for HCT-116 and MCF-7 cells, respectively, did not affect the viability of Caco-2 differentiated in normal intestinal-like cells, suggesting tumor cells as the main target of its cytotoxic action. The same compound was further investigated in order to study its mode of action. Results showed that it did not exert necrotic effects, while induced a clear shift of viable cells towards early apoptosis. Flow cytometric analysis demonstrated that this compound caused cell cycle alteration, inhibiting its progression in S and G2/M phases.
Topics: Antineoplastic Agents; Apoptosis; Caco-2 Cells; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; HCT116 Cells; Humans; MCF-7 Cells; Molecular Structure; Pyridines; Structure-Activity Relationship
PubMed: 29156549
DOI: 10.3390/molecules22112005 -
Chemical Biology & Drug Design Jul 2023MYC amplification and overexpression in breast cancer occur 16% and 22%, respectively, and MYC has a linchpin role in breast carcinogenesis. Emerging evidence has...
MYC amplification and overexpression in breast cancer occur 16% and 22%, respectively, and MYC has a linchpin role in breast carcinogenesis. Emerging evidence has started to shed light on central role of MYC in breast cancer progression. On the contrary, tumor-derived exosomes and their cargo molecules are required for the modulation of the tumor environment and to promote carcinogenesis. Still, how MYC regulates tumor-derived exosomes is still a matter of investigation in the context of breast cancer. Here, we investigated for the first time how MYC affects the biological functions of normal breast cells cocultured with exosomes derived from MYC-expression manipulated breast cancer cells. Accordingly, exosomes were isolated from MCF-7 and MDA-MB-231 cells that MYC expression was manipulated through siRNAs or lentiviral vectors by using exosome isolation reagent. Then, normal breast epithelial MCF-10A cells were treated with breast cancer cell-derived exosomes. The cellular activity of MCF-10A was investigated by cell growth assay, wound healing assay, and transwell assay. Our results suggested that MCF-10A cells treated with exosomes derived from MYC-overexpressing breast cancer cells demonstrated higher proliferation and migration capability compared with nontreated cells. Likewise, MCF-10A cells treated with exosomes derived from MYC-silenced cancer cells did not show high proliferation and invasive capacity. Overall, MYC can drive the functions of exosomes secreted from breast cancer cells. This may allow exploring a new mechanism how tumor cells regulate cancer progression and modulate tumor environment. The present study clears the way for further researches as in vivo studies and multi-omics that clarify exosomal content in an MYC-dependent manner.
Topics: Female; Humans; Breast Neoplasms; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Exosomes; MCF-7 Cells; MicroRNAs; Proto-Oncogene Proteins c-myc
PubMed: 37118982
DOI: 10.1111/cbdd.14245 -
Journal of Cancer Research and... 2016Recent studies have shown the association between statins use and cancer risk reduction. Furthermore the importance of cancer stem cells (CSCs) in tumor initiation,...
CONTEXT
Recent studies have shown the association between statins use and cancer risk reduction. Furthermore the importance of cancer stem cells (CSCs) in tumor initiation, progression and migration has been firmly established in a variety of solid tumors. Hence, the effective targeting of breast CSCs has a potential to improve cancer treatment outcome significantly.
AIMS
This study has been designed to investigation the anticancer effects of simvastatin on breast CSCs.
SETTINGS AND DESIGN
In this study, MCF-7 CSCs were isolated from parent cells and cytotoxic effects of simvastatin were evaluated and compared in both cells.
SUBJECTS AND METHODS
Stem cell isolation was done by flow cytometry technique and the effects of simvastatin on the stem cell viability, apoptosis and cell cycle were evaluated and compared with parent cells.
STATISTICAL ANALYSIS USED
The results were analyzed using one.way ANOVA, followed by Tukey.Kramer posttest. The P < 0.05 was considered as significant.
RESULTS
Based on the result, simvastatin shows dose-dependent cytotoxic effects on both CSCs and parent MCF-7 cells, whereas the apoptosis induction and the elimination of nonapoptotic programmed death were increased in CSC compared with parent cells. In addition, simvastatin showed the reduction in DNA synthesis and induced cell cycle arrest in the G1 phase in MCF-7 CSCs.
CONCLUSIONS
This finding indicates that simvastatin with specific apoptotic effect on MCF-7 CSC may provide supporting reasons for future in vivo and in vitro statin trials.
Topics: Antineoplastic Agents; Apoptosis; Biomarkers; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Flow Cytometry; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; MCF-7 Cells; Neoplastic Stem Cells; Simvastatin
PubMed: 27461641
DOI: 10.4103/0973-1482.146127