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Journal of Bioenergetics and... Dec 2020The anti-proliferative activities of Novel series of 2-(4-fluorophenyl) imidazol-5-ones against MCF-7 breast cancer cell line were explored via in-slico studies which...
The anti-proliferative activities of Novel series of 2-(4-fluorophenyl) imidazol-5-ones against MCF-7 breast cancer cell line were explored via in-slico studies which includes Quantitative structure-activity relationship QSAR, molecular docking studies, designing new compounds, and analyzing the pharmacokinetics properties of the designed compounds. From the QSAR analysis, model number one emerged the best as seen from the arithmetic assessments of (R) = 0.6981, (R) = 0.6433, (Q) = 0.5460 and (R) of 0.5357. Model number one was used in designing new derivative compounds, with higher effectiveness against estrogen positive breast cancer (MCF-7 cell line). The Molecular docking studies between the derivatives and Polo-like kinases (Plk1) receptor proved that the derivatives of 2-(4-fluorophenyl) imidazol-5-ones bind tightly to the receptor, thou ligand 24 and 27 had the highest binding affinities of -8.8 and - 9.1 kcal/mol, which was found to be higher than Doxorubicin with a docking score of -8.0 kcal/mol. These new derivatives of 2-(4-fluorophenyl) imidazol-5-ones shall be excellent inhibitors against (plk1). The pharmacokinetics analysis performed on the new structures revealed that all the structures passed the test and also the Lipinski rule of five, and they could further proceed to pre-clinical tests. They both revealed a revolution in medicine for developing novel anti-breast cancer drugs against MCF-7 cell line.
Topics: Breast Neoplasms; Cell Line, Tumor; Female; Humans; Imidazoles; MCF-7 Cells; Molecular Docking Simulation; Quantitative Structure-Activity Relationship
PubMed: 33247393
DOI: 10.1007/s10863-020-09858-0 -
Anais Da Academia Brasileira de Ciencias 2020Breast cancer is the most frequent and lethal neoplastic disease among women worldwide. Psidium Guajava is a promising functional food against cancer, owing to a variety...
Breast cancer is the most frequent and lethal neoplastic disease among women worldwide. Psidium Guajava is a promising functional food against cancer, owing to a variety of bioactive compounds. This study aimed to evaluate the anticarcinogenic potential of Pedro Sato (PS), Hitigio (HI) and Tsumori (TS) guava cultivars fruit pulp extracts in MDA-MB-435 and MCF-7 human breast cancer cells. The antioxidant capacity of the extracts and their effect on cell viability, cell cycle and apoptosis were assessed. Additionally, the concentration of carotenoids, total phenolics, ascorbic acid and other physicochemical parameters were evaluated. PS pulp extract showed the highest in vitro antioxidative activity by all tested methods, as well as the highest content of lycopene and total phenolics, while TS pulp extract presented the highest concentration of β-carotene. After 48 hours treatment, all guava cultivars' extracts caused reduction of MDA-MB-435 and MCF-7 cells viability, with PS and HI being the most effective extracts. All guava extracts caused MDA-MB-435 and MCF-7 cell count reduction in G0/G1 and G2/M phases and increased apoptosis. The present results strongly suggest that guava pulp exerts antiproliferative effect on breast adenocarcinoma cells.
Topics: Apoptosis; Breast Neoplasms; Fruit; Humans; MCF-7 Cells; Plant Extracts; Psidium
PubMed: 32813860
DOI: 10.1590/0001-3765202020191500 -
Cellular Physiology and Biochemistry :... 2015Large-scale epidemiological studies support a correlation between obesity and breast cancer in postmenopausal women. Circulating leptin levels are increased in obese and...
BACKGROUND/AIMS
Large-scale epidemiological studies support a correlation between obesity and breast cancer in postmenopausal women. Circulating leptin levels are increased in obese and it has been suggested to play a significant role in mammary tumor formation and progression. Moreover, regulation of oxidative stress is another important factor in both tumor development and responses to anticancer therapies. The aim of this study was to examine the relationship between oxidative stress and chronic leptin exposure.
METHODS
We treated MCF-7 breast cancer cells with 100 ng/mL leptin for 10 days and analyzed cell growth, ROS production and oxidative damage, as well as, some of the main antioxidant systems. Furthermore, since the hyperleptinemia has been associated with a worse pathology prognosis, we decided to test the influence of leptin in response to cisplatin anticancer treatment.
RESULTS
Leptin signalling increased cell proliferation but reduced ROS production, as well as, oxidative damage. We observed an upregulation of SIRT1 after leptin exposure, a key regulator of stress response and metabolism. Additionally, leptin counteracted cisplatin-induced cytotoxicity in tumor cells, showing a decrease in cell death.
CONCLUSION
Chronic leptin could contribute to the effective regulation of endogenous and treatment-induced oxidative stress, and it contributes to explain in part its proliferative effects.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Proliferation; Cell Survival; Cisplatin; Female; Humans; Leptin; MCF-7 Cells; Oxidative Stress; Reactive Oxygen Species; Sirtuin 1; Up-Regulation
PubMed: 25967962
DOI: 10.1159/000374066 -
Radiation and Environmental Biophysics Nov 2016Due to biocompatibility and relative non-toxic nature, gold nanoparticles (GNPs) have been studied widely to be employed in radiotherapy as radio-sensitizer. On the...
Due to biocompatibility and relative non-toxic nature, gold nanoparticles (GNPs) have been studied widely to be employed in radiotherapy as radio-sensitizer. On the other hand, they may enhance radiation-induced bystander effect (RIBE), which causes radiation adverse effects in non-irradiated normal cells. The present study was planned to investigate the possibility of augmenting the RIBE consequence of applying glucose-coated gold nanoparticles (Glu-GNPs) to target cells. Glu-GNPs were synthesized and utilized to treat MCF7 and QUDB cells. The treated cells were irradiated with 100 kVp X-rays, and their culture media were transferred to non-irradiated bystander cells. Performing MTT cellular proliferation test and colony formation assay, percentage cell viability and survival fraction of bystander cells were determined, respectively, and were compared to control bystander cells which received culture medium from irradiated cells without Glu-GNPs. Glu-GNPs decreased the cell viability and survival fraction of QUDB bystander cells by as much as 13.2 and 11.5 %, respectively (P < 0.02). However, the same end points were not changed by Glu-GNPs in MCF-7 bystander cells. Different RIBE responses were observed in QUDB and MCF7 loaded with Glu-GNPs. Glu-GNPs increased the RIBE in QUDB cells, while they had no effects on RIBE in MCF7 cells. As opposed to QUDB cells, the RIBE in MCF7 cells did not change in the dose range of 0.5-10 Gy. Therefore, it might be a constant effect and the reason of not being increased by Glu-GNPs.
Topics: Biological Transport; Bystander Effect; Glucose; Gold; Humans; MCF-7 Cells; Metal Nanoparticles
PubMed: 27613311
DOI: 10.1007/s00411-016-0669-y -
Environmental Toxicology and... Oct 2016Zinc (Zn) is an essential trace elements, its deficiency is associated with increased incidence of human breast cancer. We aimed to study the effect of Zn on human...
Zinc (Zn) is an essential trace elements, its deficiency is associated with increased incidence of human breast cancer. We aimed to study the effect of Zn on human breast cancer MCF-7 cells cultured in Zn depleted and Zn adequate medium. We found increased cancer cell growth in zinc depleted condition, further Zn supplementation inhibits the viability of breast cancer MCF-7 cell cultured in Zn deficient condition and the IC IC value for Zn is 6.2μM, 15μM, respectively after 48h. Zn markedly induced apoptosis through the characteristic apoptotic morphological changes and DNA fragmentation after 48h. In addition, Zn deficient cells significantly triggered intracellular ROS level and develop oxidative stress induced DNA damage; it was confirmed by elevated expression of CYP1A, GPX, GSK3β and TNF-α gene. Zinc depleted MCF-7 cells expressed significantly (p≤0.001) decreased levels of CDKN2A, pRb1, p53 and increased the level of mdm2 expression. Zn supplementation (IC=15μM), increased significantly CDKN2A, pRB1 & p53 and markedly reduced mdm2 expression; also protein expression levels of CDKN2A and pRb1 was significantly increased. In addition, intrinsic apoptotic pathway related genes such as Bax, caspase-3, 8, 9 & p21 expression was enhanced and finally induced cell apoptosis. In conclusion, physiological level of zinc is important to prevent DNA damage and MCF-7 cell proliferation via regulation of tumor suppressor gene.
Topics: Apoptosis; Culture Media; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p18; Cyclin-Dependent Kinase Inhibitor p21; DNA Damage; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; MCF-7 Cells; Oxidative Stress; Reactive Oxygen Species; Salivary Proline-Rich Proteins; Tumor Suppressor Protein p53; Up-Regulation; Zinc
PubMed: 27567443
DOI: 10.1016/j.etap.2016.08.002 -
International Journal of Molecular... Dec 2020Mitochondrial dysfunction plays a significant role in the metabolic flexibility of cancer cells. This study aimed to investigate the metabolic alterations due to...
UNLABELLED
Mitochondrial dysfunction plays a significant role in the metabolic flexibility of cancer cells. This study aimed to investigate the metabolic alterations due to Coenzyme Q depletion in MCF-7 cells.
METHOD
The Coenzyme Q depletion was induced by competitively inhibiting with 4-nitrobenzoate the coq2 enzyme, which catalyzes one of the final reactions in the biosynthetic pathway of CoQ. The bioenergetic and metabolic characteristics of control and coenzyme Q depleted cells were investigated using polarographic and spectroscopic assays. The effect of CoQ depletion on cell growth was analyzed in different metabolic conditions.
RESULTS
we showed that cancer cells could cope from energetic and oxidative stress due to mitochondrial dysfunction by reshaping their metabolism. In CoQ depleted cells, the glycolysis was upregulated together with increased glucose consumption, overexpression of GLUT1 and GLUT3, as well as activation of pyruvate kinase (PK). Moreover, the lactate secretion rate was reduced, suggesting that the pyruvate flux was redirected, toward anabolic pathways. Finally, we found a different expression pattern in enzymes involved in glutamine metabolism, and TCA cycle in CoQ depleted cells in comparison to controls.
CONCLUSION
This work elucidated the metabolic alterations in CoQ-depleted cells and provided an insightful understanding of cancer metabolism targeting.
Topics: Energy Metabolism; Humans; MCF-7 Cells; Mitochondria; Ubiquinone
PubMed: 33379147
DOI: 10.3390/ijms22010198 -
International Journal of Biological... Apr 2023Nanotechnology, using drug carriers, has gained remarkable achievements in treating cancer by inhibiting the adverse effects of traditional therapeutic methods, such as...
Nanotechnology, using drug carriers, has gained remarkable achievements in treating cancer by inhibiting the adverse effects of traditional therapeutic methods, such as applying curcumin. Using chitosan could help to target tumors, without harming healthy cells. Also, magnetic iron oxide provides a high specific area to increase the capability of the nano-scale vehicle to load curcumin. A double emulsion hydrogel of FeO/chitosan/agarose was synthesized and curcumin was loaded with loading and entrapment efficacies of 48.25 % and 87.5 %, respectively. The crystalline nature of the nanocomposites was confirmed by X-ray diffraction, and Fourier transforms spectroscopy investigated the functional groups of the components. The results of DLS and zeta potential showed proper particle size and surface charge, which are important for making the EPR effect and stability of the developed drug delivery system. The release profile of curcumin from the nanocarrier presented a sustained and pH-responsive release, avoiding overdosage and decreasing side effects. The best kinetic model that the release data could be fitted on was Hixon-Crowell. Finally, from the cytotoxicity of the prepared nanocomposite, it was concluded that the nanocarrier is biocompatible, and from flow cytometry analysis, a high apoptosis percentage proved that the effect of the designed drug delivery system on MCF-7 cell lines is programmed. Hence, this curcumin-loaded double emulsion could mitigate cancer therapy restrictions, with a minimum toxic effect on cultured cells.
Topics: Humans; Curcumin; Chitosan; MCF-7 Cells; Sepharose; Emulsions; Delayed-Action Preparations; Drug Carriers; Hydrogen-Ion Concentration; Drug Liberation
PubMed: 36828092
DOI: 10.1016/j.ijbiomac.2023.123786 -
Journal of the Mechanical Behavior of... Jan 2022Cells sense stiffness of surrounding tissues and adapt their activity, proliferation, motility and mechanical properties based on such interactions. Cells probe the...
Cells sense stiffness of surrounding tissues and adapt their activity, proliferation, motility and mechanical properties based on such interactions. Cells probe the stiffness of the substrate by anchoring and pulling to their surroundings, transmitting force to the extracellular matrix and other cells, and respond to the resistance they sense, mainly through changes in their cytoskeleton. Cancer and other diseases alter stiffness of tissues, and the response of cancer cells to this stiffness can also be affected. In the present study we show that MCF-7 breast cancer cells seeded on polyacrylamide gels have the ability to detect the stiffness of the substrate and alter their mechanical properties in response. MCF-7 cells plated on soft substrates display lower stiffness and viscosity when compared to those seeded on stiffer gels or glass. These differences can be associated with differences in the morphology and cytoskeleton organisation, since cells seeded on soft substrates have a round morphology, while cells seeded on stiffer substrates acquire a flat and spread morphology with formation of actin filaments, similar to that observed when seeded on glass. These findings show that MCF-7 cells can detect the stiffness of the surrounding microenvironment and thus, modify their mechanical properties.
Topics: Humans; MCF-7 Cells
PubMed: 34826769
DOI: 10.1016/j.jmbbm.2021.104979 -
Current Pharmaceutical Biotechnology 2020Vitamin C (VC) is believed to enhance immunity and is regularly integrated as a supplementary agent during several treatments.
BACKGROUND
Vitamin C (VC) is believed to enhance immunity and is regularly integrated as a supplementary agent during several treatments.
OBJECTIVE
The green (GC) and roasted (RC) coffee (Coffea arabica) aqueous extracts (0, 125, 250 and 500 μg/ml) combined with VC (50 μg/ml) were examined on the cancerous MCF-7 cell line and normal human lymphocytes.
METHODS
Neutral red uptake assay, comet assay, immunocytochemical reactivity for protein expression and mRNA expression of apoptosis-related genes were performed.
RESULTS
A significant (P< 0.05) concentration-dependent increase of apoptotic features, such as morphological changes, and abundant nuclear condensation, altered the expression of p53 and caspase-3 mRNA, down-regulation of Bcl-2 protein as well as the acidic autophagosomal vacuolization in treated cells. The oxidative stress and DNA single-strand breaks were noticed too.
CONCLUSION
These results suggest that coffee in combination with VC undergoes apoptotic anticancer pathway. This supports the integration of coffee and VC as a valuable candidate for anticancer research and treatments.
Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cell Death; Coffea; Humans; MCF-7 Cells; Plant Extracts; Seeds; Vitamins
PubMed: 31438827
DOI: 10.2174/1389201020666190822161337 -
Anti-cancer Agents in Medicinal... Nov 2017Saponins from Medicago species display several biological activities, among them apoptotic effects against plant cells have been evidenced. In contrast, their cytotoxic...
BACKGROUND
Saponins from Medicago species display several biological activities, among them apoptotic effects against plant cells have been evidenced. In contrast, their cytotoxic and antitumor activity against animal cells have not been studied in great details.
OBJECTIVE
To explore the cytotoxic properties of saponin from Medicago species against animal cells and their effect in combination with the antitumoral drug cisplatin.
METHOD
Cytotoxic activity of saponin mixtures from M. arabica (tops and roots), M. arborea (tops) and M. sativa (tops, roots and seeds) and related prosapogenins from M. arborea and M. sativa (tops) against HeLa and MCF-7 cell lines is described. In addition, cytotoxicity of soyasaponin I and purified saponins (1-8) of hederagenin, medicagenic and zanhic acid is also presented. Combination experiments with cisplatin have been also conducted.
RESULTS
Saponins from M. arabica tops and roots (mainly monodesmosides of hederagenin and bayogenin) were the most effective to reduce proliferation of HeLa and MCF-7 cell lines. Among the purified saponins, the most cytotoxic was saponin 1, 3-O-ß-D-glucopyranosyl(1→2)-α-L-arabinopyranosyl hederagenin. When saponins, derived prosapogenins and pure saponins were used in combination with cisplatin, they all, to different extent, were able to potentiate cisplatin activity against HeLa cells but not against MCF-7 cell lines. Moreover uptake of cisplatin in these cell lines was significantly reduced.
CONCLUSION
Overall results showed that specific molecular types of saponins (hederagenin glycosides) have potential as anti-cancer agents or as leads for anti-cancer agents. Moreover saponins from Medicago species have evidenced interesting properties to mediate cisplatin effects in tumor cell lines.
Topics: Antineoplastic Agents, Phytogenic; Cell Proliferation; Cisplatin; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HeLa Cells; Humans; MCF-7 Cells; Medicago; Molecular Structure; Saponins; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 28748756
DOI: 10.2174/1871520617666170727152805