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Journal of the American Chemical Society Jan 2020Effective and cell-type-specific delivery of CRISPR/Cas9 gene editing elements remains a challenging open problem. Here we report the development of biomimetic cancer...
Effective and cell-type-specific delivery of CRISPR/Cas9 gene editing elements remains a challenging open problem. Here we report the development of biomimetic cancer cell coated zeolitic imidazolate frameworks (ZIFs) for targeted and cell-specific delivery of this genome editing machinery. Coating ZIF-8 that is encapsulating CRISPR/Cas9 (CC-ZIF) with a cancer cell membrane resulted in the uniformly covered C-ZIF. Incubation of C-ZIF with MCF-7, HeLa, HDFn, and aTC cell lines showed the highest uptake by MCF-7 cells and negligible uptake by the healthy cells (i.e., HDFn and aTC). As to genome editing, a 3-fold repression in the EGFP expression was observed when MCF-7 were transfected with C-ZIF compared to 1-fold repression in the EGFP expression when MCF-7 were transfected with C-ZIF. In vivo testing confirmed the selectivity of C-ZIF to accumulate in MCF-7 tumor cells. This supports the ability of this biomimetic approach to match the needs of cell-specific targeting, which is unquestionably the most critical step in the future translation of genome editing technologies.
Topics: Animals; Biomimetics; CRISPR-Cas Systems; HeLa Cells; Heterografts; Humans; MCF-7 Cells; Metal-Organic Frameworks; Mice
PubMed: 31931564
DOI: 10.1021/jacs.9b11638 -
Molecular Pharmaceutics Aug 2020The design, synthesis, characterization, and biological activity of a series of platinum(IV) prodrugs containing the axial ligand...
The design, synthesis, characterization, and biological activity of a series of platinum(IV) prodrugs containing the axial ligand 3-(4-phenylquinazoline-2-carboxamido)propanoate () are reported. is a derivative of the quinazolinecarboxamide class of ligands that binds to the translocator protein (TSPO) at the outer mitochondrial membrane. The cytotoxicities of ,,-[Pt(NH)Cl()(OH)] (), ,,-[Pt(NH)Cl()(BZ)] (), -[Pt(DACH)(OX)()(OH)] (), and -[Pt(DACH)(OX)()(BZ)] () (DACH: ,-diaminocyclohexane, BZ: benzoate, OX: oxalate) in MCF-7 breast cancer and noncancerous MCF-10A epithelial cells were assessed and compared with those of cisplatin, oxaliplatin, and the free ligand . Moreover, the cellular uptake, ROS generation, DNA damage, and the effect on the mitochondrial function, mitochondrial membrane potential, and morphology were investigated. Molecular interactions of in the TSPO binding site were studied using molecular docking. The results showed that complex is the most effective Pt(IV) complex and exerts a multimodal mechanism involving DNA damage, potent ROS production, loss of the mitochondrial membrane potential, and mitochondrial damage.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Cisplatin; DNA Damage; Epithelial Cells; Humans; Ligands; MCF-7 Cells; Mitochondria; Mitochondrial Membranes; Organoplatinum Compounds; Oxaliplatin; Prodrugs; Reactive Oxygen Species
PubMed: 32628022
DOI: 10.1021/acs.molpharmaceut.0c00417 -
Chinese Journal of Integrative Medicine Jun 2024To evaluate the chemical composition and effects of Artemisia vulgaris (AV) hydroalcoholic extract (HEAV) on breast cancer cells (MCF-7 and SKBR-3), chronic myeloid...
OBJECTIVE
To evaluate the chemical composition and effects of Artemisia vulgaris (AV) hydroalcoholic extract (HEAV) on breast cancer cells (MCF-7 and SKBR-3), chronic myeloid leukemia (K562) and NIH/3T3 fibroblasts.
METHODS
Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass (HPLC) spectrometry. Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD, respectively. Ferrostatin-1 (Fer-1) and necrostatin-1 (Nec-1) were used to assess the mode of HEAV-induced cell death and acetoxymethylester (BAPTA-AM) was used to verify the involvement of cytosolic calcium in this event. Cytosolic calcium measurements were made using Fura-2-AM.
RESULTS
HEAV decreased the viability of MCF-7, SKBR-3 and K562 cells (P<0.05). The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts (P<0.05). Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD (P<0.05). The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone (P<0.01). HEAV-induced Ca release mainly from lysosomes in K562 cells (P<0.01). Furthermore, BAPTA-AM, an intracellular Ca chelator, decreased the number of non-viable cells treated with HEAV (P<0.05).
CONCLUSIONS
HEAV is cytotoxic and activates several modalities of cell death, which are partially dependent on lysosomal release of Ca. These effects may be related to artemisinin and caffeoylquinic acids, the main compounds identified in HEAV.
Topics: Humans; Ferroptosis; Artemisia; Animals; Mice; Plant Extracts; Necroptosis; Calcium Signaling; Lysosomes; Cell Survival; Cell Line, Tumor; NIH 3T3 Cells; K562 Cells; Calcium
PubMed: 38040876
DOI: 10.1007/s11655-023-3712-2 -
Molecules (Basel, Switzerland) Aug 2023Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of...
Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of their anti-proliferative properties is of great pharmacological interest. Some 2-alkyl-4-amino-thieno[2,3-]pyrimidines - were synthesized, and their cyto- and phototoxicity against BALB 3T3 cells were established by an in vitro 3T3 NRU test. The obtained results indicate that the tested compounds are not cytotoxic or phototoxic, and that they are appropriate to be studied for their anti-proliferative and anti-tumor properties. The anti-proliferative potential of the compounds was investigated on MCF-7 and MDA-MB-231 cancer cells, as well as a MCF-10A cell line (normal human mammary epithelial cells). The most toxic to MCF-7 was thienopyrimidine with IC 13.42 μg/mL (IC 0.045 μM), followed by compound (IC 28.89 μg/mL or IC 0.11 μM). The thienopyrimidine revealed higher selectivity to MCF-7 and lower activity (IC 367 μg/mL i.e., 1.4 μM) than compound with MCF-10A cells. With respect to MDA-MB-231 cells, ester manifested the highest effect with IC 52.56 μg/mL (IC 0.16 μM), and 2-ethyl derivative revealed IC 62.86 μg/mL (IC 0.24 μM). It was estimated that the effect of the substances on the cell cycle progression was due to cell cycle arrest in the G2 stage for MDA-MB-231, while arrest in G1 was detected for the estrogen (ER)-positive MCF-7 cell line. The tested compound's effects on the change of the zeta potential in the tumorigenic cells utilized in this study were determined. The calculation which we performed of the physicochemical properties and pharmacokinetic parameters influencing the biological activity suggested high intestinal absorption, as well as drug-likeness.
Topics: Animals; Mice; Humans; Estrogens; BALB 3T3 Cells; Carboxylic Acids; Carcinogenesis; Dermatitis, Phototoxic; MCF-7 Cells
PubMed: 37687177
DOI: 10.3390/molecules28176347 -
Natural Product Research Aug 2022The objective of this research was to evaluate the cytotoxic activities of the fractions and isolated compounds of the soft corals against A549, MCF-7 and HepG2 cell...
The objective of this research was to evaluate the cytotoxic activities of the fractions and isolated compounds of the soft corals against A549, MCF-7 and HepG2 cell lines by MTT assay method, and to chemically investigate the various metabolites of its total extract using LC-HR-ESI-MS metabolomic profiling. The metabolomic profiling revealed the presence of various metabolites, mainly sesquiterpenes and steroids reported for the first time in Additionally, eight compounds (-) have been isolated from the -hexane-chloroform (1:1) fraction that exhibited noticeable activity towards A549, MCF-7 and HepG2 cell lines. The steroids ( and ), and the sesquiterpene () exerted noticeable activity against A549 cell line (IC 28.5 ± 4.4, 36.9 ± 2.9 and 67.3 ± 9.9 µM/mL, respectively) compared to etoposide as standard cytotoxic agent (IC 48.3 ± 7.6 µM/mL). Compound also exhibited cytotoxicity against MCF-7 cell line (IC 55.3 ± 4.9 µM/mL).
Topics: Animals; Anthozoa; Antineoplastic Agents; Cell Line, Tumor; Cytotoxins; Humans; Indian Ocean; MCF-7 Cells; Sesquiterpenes; Steroids
PubMed: 34965809
DOI: 10.1080/14786419.2021.1974437 -
Molecules (Basel, Switzerland) May 2023Breast cancer is the most common type of cancer and the leading cause of cancer mortality among women worldwide. Considering the limitations of the current treatments...
Breast cancer is the most common type of cancer and the leading cause of cancer mortality among women worldwide. Considering the limitations of the current treatments available, we analyzed the in vitro cytotoxic potential of ((4-Fluoro-phenyl)-{2-[(1-phenyl-9H-β-carboline-3-carbonyl)-amino]-ethylamino}-methyl)-phosphonic acid dibutyl ester () in breast cancer cells (MCF-7 and MDA-MB-231) and in a non-tumor breast cell line (MCF-10A). has an α-aminophosphonate unit linked to the β-carboline nucleus, and the literature indicates that compounds of these classes have high biological potential. In the present study, the mechanism of action of was investigated through methods of spectrofluorimetry, flow cytometry, and protein expression analysis. It was found that inhibited the proliferation of both cancer cell lines. Furthermore, it induced oxidative stress and cell cycle arrest in G2/M. Upregulation of apoptosis-related proteins such as Bax, cytochrome C, and caspases, as well as a decrease in the anti-apoptotic protein Bcl-2, indicated potential induction of apoptosis in the MDA-MB-231 cells. While in MCF-7 cells, activated the autophagic death pathway, which was demonstrated by an increase in autophagic vacuoles and acidic organelles, in addition to increased expression of LC3I/LC3II and reduced SQSTM1/p62 expression. Further, demonstrated antimetastatic potential by reducing MMP-9 expression and cell migration in both breast cancer cell lines. In conclusion, is a promising candidate for breast cancer chemotherapy.
Topics: Female; Humans; Breast Neoplasms; Antineoplastic Agents; Cell Cycle Checkpoints; MCF-7 Cells; Apoptosis; Apoptosis Regulatory Proteins; Carbolines; Cell Proliferation; Cell Line, Tumor
PubMed: 37175359
DOI: 10.3390/molecules28093949 -
Proceedings of the National Academy of... Sep 2021Extracellular vesicles (EVs) are constantly secreted from both eukaryotic and prokaryotic cells. EVs, including those referred to as exosomes, may have an impact on cell...
Extracellular vesicles (EVs) are constantly secreted from both eukaryotic and prokaryotic cells. EVs, including those referred to as exosomes, may have an impact on cell signaling and an incidence in diseased cells. In this manuscript, a platform to capture, quantify, and phenotypically classify the EVs secreted from single cells is introduced. Microfluidic chambers of about 300 pL are employed to trap and isolate individual cells. The EVs secreted within these chambers are then captured by surface-immobilized monoclonal antibodies (mAbs), irrespective of their intracellular origin. Immunostaining against both plasma membrane and cytosolic proteins was combined with highly sensitive, multicolor total internal reflection fluorescence microscopy to characterize the immobilized vesicles. The data analysis of high-resolution images allowed the assignment of each detected EV to one of 15 unique populations and demonstrated the presence of highly heterogeneous phenotypes even at the single-cell level. The analysis also revealed that each mAb isolates phenotypically different EVs and that more vesicles were effectively immobilized when CD63 was targeted instead of CD81. Finally, we demonstrate how a heterogeneous suppression in the secreted vesicles is obtained when the enzyme neutral sphingomyelinase is inhibited.
Topics: Biological Transport; Biomarkers; Cell Line, Tumor; Cell Membrane; Exosomes; Extracellular Vesicles; Humans; MCF-7 Cells; Membrane Proteins; Phenotype
PubMed: 34518226
DOI: 10.1073/pnas.2106630118 -
Anti-cancer Agents in Medicinal... 2022Breast cancer (BC) is one of the most frequent malignancies and the most common reasons for impermanence in women. The backbone of therapy for BC is principally... (Review)
Review
INTRODUCTION
Breast cancer (BC) is one of the most frequent malignancies and the most common reasons for impermanence in women. The backbone of therapy for BC is principally chemotherapy, but its non-specific nature to differentiate between normal cells and cancer cells and severe side effects are the main barriers in its use. So, there is an intense requirement to enlarge more efficacious, more specific and safer anti-BC agents.
OBJECTIVE
Isatin (IST) is an endogenous molecule that is a principal class of heterocyclic compounds and exhibits a wide range of therapeutic activities which can be used as a starting material for the synthesis of several drug molecules. Many kinds of literature were reported previously on different pharmacological activities of IST derivatives and particularly on anticancer activity but this review mainly focuses on anti-BC activities of IST derivatives through MCF-7, MDA MB 231, MDA-MB 435 and MDA-MB 468 cell lines. Herein we mentioned; a total of 33 IST derivatives (compound 24- 56) which show good anti-BC activity. IST-derived compounds are also available in the market and are used for various cancer types like sunitinib for renal cell carcinoma (RCC) and Nintedanib for the cryptogenic fibrosing alveolitis treatment, but when evaluated for BC, they did not prove to be much successful.
CONCLUSION
This review mainly highlights anti-BC activities of various IST analogues using MCF-7, MDA MB 231, MDA-MB 435 and MDA-MB 468 cell lines, displaying the potent compound of the series and structure-activity relationships of compounds with molecular docking also. So, this study mainly shows the importance of IST as a major source for drug design and development of newer anti-BC drugs.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Female; Humans; Isatin; MCF-7 Cells; Molecular Docking Simulation; Molecular Structure
PubMed: 34477529
DOI: 10.2174/1871520621666210903130152 -
Nutrients Jun 2023Rutin has been reported as a potential anti-cancer agent for several decades. This study evaluated the effects of rutin on the proliferation, metastasis, and...
Rutin has been reported as a potential anti-cancer agent for several decades. This study evaluated the effects of rutin on the proliferation, metastasis, and angiogenesis of MDA-MB-231 and MCF-7 breast cancer cell lines. Increasing concentrations of rutin significantly stimulated the proliferation of MDA-MB-231 and MCF-7 cells compared to controls. Wound scratch assay demonstrated that rutin had an inducing effect on the migration of the cells. In MDA-MB-231 and MCF-7 cells, rutin upregulated MKI67, VIM, CDH2, FN1, and VEGFA and downregulated CDH1 and THBS1 genes. It also increased N-cadherin and VEGFA and decreased E-cadherin and thrombospondin 1 protein expression. Our data indicated that rutin could stimulate proliferation, migration, and pro-angiogenic activity in two different breast cancer cell lines. This phytoestrogen induced invasion and migration of both cell lines by a mechanism involving the EMT process. This suggests that rutin may act as a breast-cancer-promoting phytoestrogen.
Topics: Humans; Female; Epithelial-Mesenchymal Transition; MCF-7 Cells; Cell Line, Tumor; Breast Neoplasms; Phytoestrogens; Cell Movement; Cell Proliferation
PubMed: 37447209
DOI: 10.3390/nu15132884 -
Molecules (Basel, Switzerland) Jun 2022Our previous findings have shown that the chlorophyllides composites have anticancer activities to breast cancer cell lines (MCF-7 and MDA-MB-231). In the present study,...
Our previous findings have shown that the chlorophyllides composites have anticancer activities to breast cancer cell lines (MCF-7 and MDA-MB-231). In the present study, microarray gene expression profiling was utilized to investigate the chlorophyllides anticancer mechanism on the breast cancer cells lines. Results showed that chlorophyllides composites induced upregulation of 43 and 56 differentially expressed genes (DEG) in MCF-7 and MDA-MB-231 cells, respectively. In both cell lines, chlorophyllides composites modulated the expression of annexin A4 (ANXA4), chemokine C-C motif receptor 1 (CCR1), stromal interaction molecule 2 (STIM2), ethanolamine kinase 1 (ETNK1) and member of RAS oncogene family (RAP2B). Further, the KEGG annotation revealed that chlorophyllides composites modulated DEGs that are associated with the endocrine system in MCF-7 cells and with the nervous system in MDA-MB-231 cells, respectively. The expression levels of 9 genes were validated by quantitative reverse transcription PCR (RT-qPCR). The expression of CCR1, STIM2, ETNK1, MAGl1 and TOP2A were upregulated in both chlorophyllides composites treated-MCF-7 and MDA-MB-231 cells. The different expression of NLRC5, SLC7A7 and PKN1 provided valuable information for future investigation and development of novel cancer therapy.
Topics: Amino Acid Transport System y+L; Breast; Breast Neoplasms; Cell Line, Tumor; Chlorophyllides; Early Detection of Cancer; Female; Humans; Intracellular Signaling Peptides and Proteins; MCF-7 Cells; rap GTP-Binding Proteins
PubMed: 35745070
DOI: 10.3390/molecules27123950