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Chemical & Pharmaceutical Bulletin Dec 2018The work reported the design and cytotoxic screening of synthetic small molecules: carbonitriles 3a-c, carboximidamides 4a-c, and oxadiazoles 5-19 as antitumor...
The work reported the design and cytotoxic screening of synthetic small molecules: carbonitriles 3a-c, carboximidamides 4a-c, and oxadiazoles 5-19 as antitumor molecules. Molecules 4c, 9, 12, and 14 show promising cytotoxicity profiles against two cell lines higher than prodigiosin (PG). The results of topoisomerase enzyme inhibition assay show that carboximidamide 4c and oxadiazole 14 display potent inhibitory activity in nano-molar concentration higher than PG. In addition, carboximidamide 4c and oxadiazoles 9, 12, and 14 exhibit antiproliferative activities over MCF-7 cells by cell cycle arrest at G phase and apoptosis inducing activity by increasing cell population percentages at pre G and G/M phases as shown by DNA-flow cytometry assay and annexin V analysis. Moreover, measurement of p53 and cell death mediators, show that carboximidamide 4c and oxadiazoles 9, 12, and 14 significantly up-regulate p53, Puma and Bax/Bcl-2 ratio levels. Subsequently, pro-apoptotic activities are confirmed by active caspase 3/7 percentages green fluorescence assay.
Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Proliferation; Dose-Response Relationship, Drug; Drug Design; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Humans; MCF-7 Cells; Molecular Structure; Oxadiazoles; Structure-Activity Relationship
PubMed: 30298827
DOI: 10.1248/cpb.c18-00636 -
Molecules (Basel, Switzerland) Feb 2022Three-dimensional cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions. The surface...
Three-dimensional cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions. The surface hydrophobicity strongly influences the promotion of cell aggregate formation. In particular, for spheroid formation, highly water-repellent coatings seem to be required for the significant effects of the process. In this work, surfaces at different wettability have been compared to observe their influence on the growth and promotion of aggregates of representative mammalian cell lines, both tumoral and non-tumoral (3T3, HaCat and MCF-7 cell lines). The effect of increased hydrophobicity from TCPS to agarose hydrogel to mixed organic-inorganic superhydrophobic (SH) coating has been investigated by optical and fluorescence microscopy, and by 3D confocal profilometry, in a time scale of 24 h. The results show the role of less wettable substrates in inducing the formation of spheroid-like cell aggregates at a higher degree of sphericity for the studied cell lines.
Topics: 3T3 Cells; Animals; Cell Culture Techniques; Cell Proliferation; Humans; Hydrogels; Hydrophobic and Hydrophilic Interactions; MCF-7 Cells; Mice; Spheroids, Cellular
PubMed: 35209035
DOI: 10.3390/molecules27041247 -
Environment International Jun 2024With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become...
With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become a hot topic of research. However, investigations into their endocrine-disrupting toxicity under combined binary exposure, especially the molecular mechanism of combined effects, have rarely been documented. In this study, two typical EDCs, perfluorooctanoic acid (PFOA) and 4-hydroxybenzophenone (4-HBP), were selected to examine their combined effects and molecular mechanism on MCF-7 cell proliferation at environmentally relevant exposure concentrations. We have successfully established a model to evaluate the binary combined toxic effects of endocrine disruptors, presenting combined effects in a simple and direct way. Results indicated that the combined effect changed from additive to synergistic from 1.25 × 10 M to 4 × 10 M. Metabolomics analyses suggested that exposure to PFOA and 4-HBP caused significant alterations in purine metabolism, arginine, and proline metabolism and had superimposed influences on metabolism. Enhanced combined effects were observed in glycine, serine, and threonine metabolic pathways compared to exposure to PFOS and 4-HBP alone. Additionally, the differentially expressed genes (DEGs) are primarily involved in Biological Processes, especially protein targeting the endoplasmic reticulum, and significantly impact the oxidative phosphorylation and thermogenesis-related KEGG pathway. By integrating metabolome and transcriptome analyses, PFOA and 4-HBP regulate purine metabolism, the TCA cycle, and endoplasmic reticulum protein synthesis in MCF-7 cells via mTORC1, which provides genetic material, protein, and energy for cell proliferation. Furthermore, molecular docking confirmed the ability of PFOA and 4-HBP to stably bind the estrogen receptor, indicating that they have different binding pockets. Collectively, these findings will offer new insights into understanding the mechanisms by which EDCs produce combined toxicity.
Topics: Humans; Caprylates; MCF-7 Cells; Endocrine Disruptors; Fluorocarbons; Cell Proliferation; Parabens; Metabolomics; Multiomics
PubMed: 38815467
DOI: 10.1016/j.envint.2024.108778 -
Journal of Applied Biomaterials &... 2022Analyze the antitumor capacity of cetylpyridinium chloride (CPC) on human breast tumor cells, and the possible action mechanism.
OBJECTIVE
Analyze the antitumor capacity of cetylpyridinium chloride (CPC) on human breast tumor cells, and the possible action mechanism.
MATERIAL AND METHODS
The human breast tumor cells MCF-7 and no-tumor breast cells MCF-10A were exposed to CPC under various condition (concentration and duration). Cell viability was measured with MTT assay, the LIVE/DEAD assay, and fluorescence microscopy. Membrane permeability after CPC exposure was evaluated by Calcein AM assay, mitochondrial morphology with a MitoView staining, and genotoxicity with the comet assay and fluorescence microscopy.
RESULTS
CPC was cytotoxic to both MCF-7 and MCF-10A as of a 24-h exposure to 0.1 µM. Cytotoxicity was dose-dependent and reached 91% for MCF-7 and 78% for MCF-10A after a 24-h exposure to 100 µM CPC, which outperformed the positive control doxorubicin in effectiveness and selectivity. The LD50 of CPC on was 6 µM for MCF-7 and 8 µM for MCF-10A, yielding a selectivity index of 1.41. A time response analysis revealed 64% dead cells after only 5 min of exposure to 100 µM CPC. With respect to the action mechanisms, the comet assay did not reveal genome fragmentation. On the other hand, membrane damage was dose-dependent and may also affect mitochondrial morphology.
CONCLUSION
Cetylpyridinium chloride inhibits MCF-7 cell growing in a non-selective way as of 5 min of exposure. The action mechanism of CPC on tumor cells involves cell membrane damage without change neither mitochondrial morphology nor genotoxicity.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Survival; Cetylpyridinium; Female; Humans; MCF-7 Cells
PubMed: 35485910
DOI: 10.1177/22808000221092157 -
Asian Pacific Journal of Cancer... 2016Crocus sativus and its major constituent crocin are well established to have anti-cancer properties in breast cancer cells (MCF-7). However the role of C. sativus...
BACKGROUND
Crocus sativus and its major constituent crocin are well established to have anti-cancer properties in breast cancer cells (MCF-7). However the role of C. sativus extract (CSE) and crocin on caspase signaling mediated MCF-7 cell death at molecular level is remains unclear. In this study, we tried to unravel role of CSE and crocin on caspase mediated MCF-7 cells death and their in vivo preclinical toxicity profiling and immune stimulatory effect.
MATERIALS AND METHODS
CSE extract was fractionated by HPLC and crocin was isolated and characterized by NMR, IR, and MS. MCF-7 cells were treated with both CSE and crocin and expression of Bcl-2 and Bax was assessed after 24 and 36 hours. Furthermore, caspase 3, caspase 8 and caspase 9 expression was determined by Western blotting after 24 hours of treatment. DNA fragmentation analysis was performed for genotoxicity of CSE and crocin in MCF-7 cells. The in vivo toxicity profile of CSE (300 mg/kg of b.wt) was investigated in normal Swiss albino mice. In addition, peritoneal macrophages were collected from crocin (1, 1.5 and 2 mg/kg body weight) treated mice and analyzed for ex vivo yeast phagocytosis.
RESULTS
Immunoblot analysis revealed that there was time dependent decline in anti-apoptotic Bcl-2 with simultaneous upregulation of Bax in CSE and crocin treated MCF-7 cells. Further CSE and crocin treatment downregulated caspase 8 and 9 and cleaved the caspase 3 after 24 hours. Both CSE and crocin elicited considerable DNA damage in MCF-7 cells at each concentration tested. In vivo toxicity profile by histological studies revealed no observable histopathologic differences in the liver, kidney, spleen, lungs and heart in CSE treated and untreated groups. Crocin treatment elicited significant dose and time dependent ex vivo yeast phagocytosis by peritoneal macrophages.
CONCLUSIONS
Our study delineated involvement of pro-apoptotic and caspase mediated MCF-7 cell death by CSE and crocin at the molecular level accompanied with extensive DNA damage. Further we found that normal swiss albino mice can tolerate the maximum dose of CSE. Crocin enhanced ex vivo macrophage yeast phagocytic ability.
Topics: Animals; Apoptosis; Blotting, Western; Carotenoids; Caspases; Cell Proliferation; Crocus; DNA Damage; Flow Cytometry; Humans; MCF-7 Cells; Macrophage Activation; Macrophages, Peritoneal; Male; Mice; Plant Extracts
PubMed: 27039797
DOI: 10.7314/apjcp.2016.17.3.1499 -
Marine Drugs May 2018A new sesquiterpenoid 9,10-diolhinokiic acid () and a new diterpenoid roussoellol C (), together with 4 known compounds, were isolated from the extracts of laboratory...
A new sesquiterpenoid 9,10-diolhinokiic acid () and a new diterpenoid roussoellol C (), together with 4 known compounds, were isolated from the extracts of laboratory cultures of marine-derived fungus . 9,10-diolhinokiic acid is the first thujopsene-type sesquiterpenoid containing a 9,10-diol moiety, and roussoellol C possesses a novel tetracyclic fusicoccane framework with an unexpected hydroxyl at C-4. These new structures were confirmed by spectroscopic data, chemical method, NMR data calculations and electronic circular dichroism (ECD) calculations. The selected compounds were evaluated for cytotoxicities against five human cancer cell lines, including SW480, HL-60, A549, MCF-7, and SMMC-7721 and the IC values of compound against MCF-7 and against HL-60 cells were 6.5 and 7.9 μM, respectively.
Topics: A549 Cells; Cell Line, Tumor; HL-60 Cells; Humans; MCF-7 Cells; Sesquiterpenes; Talaromyces; Terpenes
PubMed: 29724060
DOI: 10.3390/md16050150 -
Asian Pacific Journal of Cancer... 2016Breast cancer is the most common malignancy and also the second leading cause of cancer death among women and also in women that have a high mortality. Previous studies...
Breast cancer is the most common malignancy and also the second leading cause of cancer death among women and also in women that have a high mortality. Previous studies showed that magnesium (Mg) has cytotoxic effects on malignant cell lines. However, the anti-cancer effects of Mg on MCF-7 breast cancer cells are uncertain. This study was aimed at the comparison of the cytotoxic effect of Mg salt (MgCl2) and cisplatin on MCF-7 cells and fibroblasts (as normal cells). After treatment with various concentrations of MgCl2, and cisplatin as a positive control for 24 and 48 hours (h), cytotoxicity activity was measured by MTT assay. In addition, apoptosis was determined by annexin V/propidium iide assay. Both cisplatin and the MgCl2 exhibited dose-dependent cytotoxic effects in the MCF-7 cell line, although the LD50 of the Mg was significantly higher when compared to cispaltin (40 μg/ml vs. 20 μg/ml). Regarding annexin V/propidium results, treatment of MCF-7 cells with LD50 concentrations of cisplatin and Mg showed 59% and 44% apoptosis at 24h, respectively. Finally, the results indicated that Mg has cytotoxic effects on MCF-7 cells, but less than cisplatin as a conventional chemotherapeutic agent. However, regarding the side effects of chemotherapy drugs, it seems that Mg can be considered as a supplement for the treatment of breast cancer.
Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Proliferation; Cisplatin; Drug Therapy, Combination; Female; Flow Cytometry; Humans; MCF-7 Cells; Magnesium Chloride
PubMed: 27165250
DOI: 10.7314/apjcp.2016.17.s3.131 -
Anticancer Research Dec 2021Effect of capsicodendrin on the NF-κB pathway was studied in MCF-7 cancer cells.
BACKGROUND/AIM
Effect of capsicodendrin on the NF-κB pathway was studied in MCF-7 cancer cells.
MATERIALS AND METHODS
The transcription factor assay was used to screen for NF-κB activity. The effect on IKKβ, ICAM-1, and caspase-7 were studied using western blot. Caspase-1 was studied using Promega Caspase-Glo assay. Reactive oxygen species (ROS) were detected using the fluorescent probe DCFH-DA. The potentiometric dye JC-1 was used to assess mitochondrial membrane potential (ΔΨm) and the cell cycle was examined using a fluorescence-activated cell sorter.
RESULTS
NF-κB p65 inhibitory effect was IC=8.6 μM and cytotoxic activity was IC=7.5 μM. The upstream IKK and the downstream ICAM-1 were down-regulated. Sub G-phase population increased to 81% after 12 h of treatment with capsicodendrin (10 μM) and there was no loss of ΔΨM.
CONCLUSION
Increased levels of intracellular ROS promoted activity of caspase-1 and induced cell death in MCF-7 cells. Capsicodendrin may be a future anticancer agent that prevents the progression of metastatic breast cancer.
Topics: Antineoplastic Agents, Phytogenic; Caspases; Cell Cycle; Cinnamomum; Female; Humans; I-kappa B Kinase; MCF-7 Cells; Membrane Potential, Mitochondrial; Molecular Structure; NF-kappa B; Plant Extracts; Reactive Oxygen Species; Signal Transduction
PubMed: 34848447
DOI: 10.21873/anticanres.15412 -
Forensic Toxicology Jul 2023The effects of extended Δ-tetrahydrocannabinol (Δ-THC) exposure on estrogen receptor-positive human breast cancer MCF-7 cells have been investigated; however, the...
PURPOSE
The effects of extended Δ-tetrahydrocannabinol (Δ-THC) exposure on estrogen receptor-positive human breast cancer MCF-7 cells have been investigated; however, the effects of Δ-THC exposure for a shorter duration remain unclear. In this study, we sought to study whether Δ-THC stimulates the migration of MCF-7 cells under both estrogenic and estrogen-deprived conditions over a short period (approximately 6 h).
METHODS
MCF-7 cells were treated with Δ-THC under estrogenic or estrogen-deprived conditions, and cell migration was subsequently analyzed.
RESULTS
Δ-THC-stimulated migration of MCF-7 cells 6 h after exposure was only observed in the estrogen-deprived condition. However, Δ-THC-mediated migration was counteracted under estrogenic conditions without affecting cell proliferation and estrogen receptor expression during this period.
CONCLUSIONS
Δ-THC can stimulate MCF-7 cell migration under estrogen-deprived conditions; however, there is an interfering interaction between Δ-THC and the estrogenic milieu that influences the migration of MCF-7 cells.
Topics: Humans; Female; Breast Neoplasms; Dronabinol; Receptors, Estrogen; MCF-7 Cells; Estrogens; Estrone; Cell Movement
PubMed: 36583834
DOI: 10.1007/s11419-022-00655-5 -
Nutrients Mar 2023Drug resistance is a well-known and significant obstacle in the battle against cancer, rendering chemotherapy treatments often ineffective. To improve the effectiveness...
Drug resistance is a well-known and significant obstacle in the battle against cancer, rendering chemotherapy treatments often ineffective. To improve the effectiveness of chemotherapy, researchers are exploring the use of natural molecules that can enhance its ability to kill cancer cells and limit their spread. Docosahexaenoic acid (DHA), a lipid found in marine fish, has been shown to enhance the cytotoxicity of various anti-cancer drugs in vitro and in vivo. While the combined use of chemotherapeutic drugs with DHA demonstrated promising preliminary results in clinical trials, there is still a significant amount of information to be discovered regarding the precise mechanism of action of DHA. As the biological pathways involved in the chemosensitization of already chemoresistant MCF-7 cells are still not entirely unraveled, in this study, we aimed to investigate whether DHA co-treatment could enhance the ability of the chemotherapy drug doxorubicin to inhibit the growth and invasion of MCF-7 breast cancer cells (MCF-7/Dox) that had become resistant to the drug. Upon treating MCF-7/Dox cells with DHA or DHA-doxorubicin, it was observed that the DHA-doxorubicin combination effectively enhanced cancer cell death by impeding in vitro propagation and invasive ability. In addition, it led to an increase in doxorubicin accumulation and triggered apoptosis by arresting the cell cycle at the G2/M phase. Other observed effects included a decrease in the multi-drug resistance (MDR) carrier P-glycoprotein (P-gp) and TG2, a tumor survival factor. Augmented quantities of molecules promoting apoptosis such as Bak1 and caspase-3 and enhanced lipid peroxidation were also detected. Our findings in the cell model suggest that DHA can be further investigated as a natural compound to be used alongside doxorubicin in the treatment of breast cancer that is unresponsive to chemotherapy.
Topics: Humans; Animals; Female; MCF-7 Cells; Docosahexaenoic Acids; Drug Resistance, Neoplasm; Doxorubicin; Antineoplastic Agents; Breast Neoplasms; Apoptosis; Cell Line, Tumor
PubMed: 37049499
DOI: 10.3390/nu15071658