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Nutrients Feb 2022L. (fenugreek), a member of the legume family (Fabaceae), is a promising source of bioactive phytochemicals, which explains its traditional use for a variety of...
L. (fenugreek), a member of the legume family (Fabaceae), is a promising source of bioactive phytochemicals, which explains its traditional use for a variety of metabolic disorders including cancer. The current study aimed to evaluate extracts of fenugreek seeds and sprouts, and some of their constituents, to compare their cytotoxic and antiproliferative activities in MCF-7 breast cancer cells. The extracts were chemically characterised using high-resolution accurate mass liquid chromatography-mass spectrometry to reveal the detection of compounds assigned as flavone -glycosides including those derived from apigenin and luteolin, in addition to isoflavones. Five different flavones or their glycosides (apigenin, vicenin-2, vitexin, luteolin and orientin) and two isoflavones (daidzein and formononetin) were quantified in the fenugreek extracts. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using MCF-7 cells treated with fenugreek methanolic extracts showed dose- and time-dependent effects on cell viability. The MCF-7 cancer cells treated with the fenugreek methanolic extracts also displayed increased relative mitochondrial DNA damage as well as suppressed metastasis and proliferation. This study demonstrates the potential anti-cancer effects of fenugreek seeds and sprouts and reveals fenugreek sprouts as an untapped resource for bioactive compounds.
Topics: Breast Neoplasms; Female; Humans; MCF-7 Cells; Plant Extracts; Seeds; Trigonella
PubMed: 35215434
DOI: 10.3390/nu14040784 -
Anticancer Research Apr 2022The anticancer potential of indomethacin and diclofenac has been reported against several types of cancer cells. In this study, we investigated the enhancement effect of...
BACKGROUND/AIM
The anticancer potential of indomethacin and diclofenac has been reported against several types of cancer cells. In this study, we investigated the enhancement effect of a coumaric acid derivative found in some Piper plants, N-trans-p-coumaroyltyramine (TCT) on indomethacin and diclofenac cytotoxicity in breast cancer cells.
MATERIALS AND METHODS
MCF-7 and mitoxantrone-resistant MCF-7 (MCF-7/MX) cancer cells were treated with indomethacin or diclofenac in the presence of TCT for 48 h. Cell viability, apoptosis, mitochondrial function and signaling proteins were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Hoechst 33342, tetramethyl-rhodamine-ethyl-ester and western blot analysis, respectively.
RESULTS
Combination treatment resulted in significant reduction of cell viability and mitochondrial membrane potential, whereas the ratio of BCL2-associated X, apoptosis regulator to BCL2 apoptosis regulator, and apoptosis increased. The enhancing effect of TCT was related to reduced nuclear factor-erythroid factor 2-related factor 2/heme oxygenase-1 expression, and increased activation of the protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2 alpha/activating transcription factor 4/C/EBP homologous protein signaling pathways.
CONCLUSION
TCT in combination with indomethacin or diclofenac promoted endoplasmic reticulum stress-dependent apoptosis in breast cancer cells.
Topics: Apoptosis; Coumaric Acids; Diclofenac; Endoplasmic Reticulum Stress; Humans; Indomethacin; MCF-7 Cells
PubMed: 35347001
DOI: 10.21873/anticanres.15659 -
Scientific Reports Dec 2023Breast cancer (BC) is one of the leading causes of cancer-related deaths in women. The present study explored the potential role of pseudogenes in BC via construction...
Breast cancer (BC) is one of the leading causes of cancer-related deaths in women. The present study explored the potential role of pseudogenes in BC via construction and analysis of a competing endogenous RNA (ceRNA) network through a three-step process. First, we screened differentially expressed genes in nine BC datasets. Then the gene-pseudogenes pairs (nine hub genes) were selected according to the functional enrichment and correlation analysis. Second, the candidate hub genes and interacting miRNAs were used to construct the ceRNA network. Further analysis of the ceRNA network revealed a crucial ceRNA module with two genes-pseudogene pairs and two miRNAs. The in-depth analysis identified the GBP1/hsa-miR-30d-5p/GBP1P1 axis as a potential tumorigenic axis in BC patients. In the third step, the GBP1/hsa-miR-30d-5p/GBP1P1 axis expression level was assessed in 40 tumor/normal BC patients and MCF-7 cell lines. The expression of GBP1 and GBP1P1 was significantly higher in the tumor compared to the normal tissue. However, the expression of hsa-miR-30d-5p was lower in tumor samples. Then, we introduced the GBP1P1 pseudogene into the MCF-7 cell line to evaluate its effect on GBP1 and hsa-miR-30d-5p expression. As expected, the GBP1 level increased while the hsa-miR-30d-5p level decreased in the GBP1P1-overexprsssing cell line. In addition, the oncogenic properties of MCF-7 (cell viability, clonogenicity, and migration) were improved after GBP1P1 overexpression. In conclusion, we report a ceRNA network that may provide new insight into the role of pseudogenes in BC development.
Topics: Humans; Female; Breast Neoplasms; Pseudogenes; RNA, Competitive Endogenous; MicroRNAs; MCF-7 Cells
PubMed: 38072995
DOI: 10.1038/s41598-023-49110-4 -
International Journal of Molecular... Dec 2022A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized. An MTT assay revealed that most of tested hybrids showed more enhanced...
A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized. An MTT assay revealed that most of tested hybrids showed more enhanced anti-proliferative activities than artemisinin, among which A8 had the superior potency with IC values ranging from 4.07 μM to 9.71 μM against five tested cancer cell lines. Cell colony formation assays showed that A8 could inhibit significantly more cell proliferation than artemisinin and 5-fluorouracil. Further mechanism studies reveal that A8 induces apoptosis and ferroptosis in MCF-7 cells in a dose-dependent manner, and CYPs inhibition assays reveal that A8 has a moderate inhibitory effect on CYP1A2 and CYP3A4 in the human body at 10 μM. The present work indicates that hybrid A8 may merit further investigation as a potential therapeutic agent.
Topics: Humans; MCF-7 Cells; Molecular Structure; Ferroptosis; Antineoplastic Agents; Drug Screening Assays, Antitumor; Apoptosis; Artemisinins; Cell Proliferation; Structure-Activity Relationship; Cell Line, Tumor
PubMed: 36555409
DOI: 10.3390/ijms232415768 -
Chemistry & Biodiversity Dec 2023A library of 6-(((1-(substitutedphenyl)-1H-1,2,3-triazol-4-yl)methyl) amino)-3-methylquinazolin-4(3H)-one analogues synthesized from Isatin precursor through a series of...
A library of 6-(((1-(substitutedphenyl)-1H-1,2,3-triazol-4-yl)methyl) amino)-3-methylquinazolin-4(3H)-one analogues synthesized from Isatin precursor through a series of nitration, reduction, hydrolysis, cyclization and click reaction. The structures of compounds were characterized by spectral data including IR, H-NMR, C NMR and Mass. The novel quinazolinone - 1,2,3-triazoles were screened for their cytotoxicity against the human breast adenocarcinoma cell lines MCF-7 by MTT assay. 4-Isopropyl and 2-bromo substituted analogues executed high activity against MCF-7 cell line with IC value of 10.16±0.07 μM and 11.23±0.20 μM compared to the Doxorubicin whose IC value is 10.81±0.03 μM. The activity of remaining compounds is good to moderate. Further, the molecular docking studies against the crystal structure of Epidermal Growth Factor Receptor delivered the best binding energies and the interactions such as H-bond and hydrophobic are inevitable. The predicted pharmacokinetic properties results showed that these compounds have more drug likeness properties.
Topics: Humans; MCF-7 Cells; Molecular Structure; Structure-Activity Relationship; Triazoles; Quinazolinones; Antineoplastic Agents; Cell Line, Tumor; Molecular Docking Simulation; Cell Proliferation
PubMed: 37708234
DOI: 10.1002/cbdv.202300800 -
Journal of Translational Medicine Mar 2023Breast cancer is the second leading cause of death among women after lung cancer. Despite the improvement in prevention and in therapy, breast cancer still remains a...
BACKGROUND
Breast cancer is the second leading cause of death among women after lung cancer. Despite the improvement in prevention and in therapy, breast cancer still remains a threat, both for pre- and postmenopausal women, due to the development of drug resistance. To counteract that, novel agents regulating gene expression have been studied in both hematologic and solid tumors. The Histone Deacetylase (HDAC) inhibitor Valproic Acid (VA), used for epilepsy and other neuropsychiatric diseases, has been demonstrated a strong antitumoral and cytostatic activity. In this study, we tested the effects of Valproic Acid on the signaling pathways involved in breast cancer cells viability, apoptosis and in Reactive Oxygen Species (ROS) production using ER-α positive MCF-7 and triple negative MDA-MB-231 cells.
METHODS
Cell proliferation assay was performed by MTT Cell cycle, ROS levels and apoptosis were analyzed by flow cytometry, protein levels were detected by Western Blotting.
RESULTS
Cell treatment with Valproic Acid reduced cell proliferation and induced G0/G1 cell cycle arrest in MCF-7 and G2/M block in MDA-MB-231 cells. In addition, in both cells the drug enhanced the generation of ROS by the mitochondria. In MCF-7 treated cells, it has been observed a reduction in mitochondrial membrane potential, a down regulation of the anti-apoptotic marker Bcl-2 and an increase of Bax and Bad, leading to release of cytochrome C and PARP cleavage. Less consistent effects are recorded in MDA-MB-231 cells, in which the greater production of ROS, compared to MCF-7cells, involves an inflammatory response (activation of p-STAT3, increased levels of COX2).
CONCLUSIONS
Our results have demonstrated that in MCF-7 cells the Valproic Acid is a suitable drug to arrest cell growth, to address apoptosis and mitochondrial perturbations, all factors that are important in determining cell fate and health. In a triple negative MDA-MB 231 cells, valproate directs the cells towards the inflammatory response with a sustained expression of antioxidant enzymes. Overall, the not always unequivocal data between the two cellular phenotypes indicate that further studies are needed to better define the use of the drug, also in combination with other chemotherapy, in the treatment of breast tumors.
Topics: Female; Humans; Valproic Acid; MCF-7 Cells; Reactive Oxygen Species; Cell Cycle; Cell Proliferation; Histone Deacetylase Inhibitors
PubMed: 36864445
DOI: 10.1186/s12967-023-04015-8 -
Journal of Microencapsulation 2021Hesperidin, a ubiquitous plant-based flavanone, was encapsulated into nanoemulsions (HP-NEM) using a spontaneous emulsification method to improve its solubility and...
Hesperidin, a ubiquitous plant-based flavanone, was encapsulated into nanoemulsions (HP-NEM) using a spontaneous emulsification method to improve its solubility and enhance bioavailability and efficacy in breast cancer treatment using MCF-7 cell lines. The cytotoxic and apoptotic effects of HP-NEM against MCF-7 and its impact on oncomiRs, microRNA-21, and microRNA-155 expression were also assessed. The optimised HP-NEM displayed a spherical shape with 305 ± 40.8 nm, 0.308 ± 0.04, and -11.6 ± 3.30 mV and 93 ± 0.45% for particle size, polydispersity index (PDI), zeta-potential (ζ), and encapsulation efficiency, respectively. Cytotoxicity studies using MTT assay showed selective toxicity of the HP-NEM against MCF-7 without affecting normal cells (HEK 293). Treatment with the HP-NEM induced cell death through apoptosis, cell cycle arrest in the G2/M phase, and downregulated miR-21 and miR-155 expression in MCF-7. This study supports the use of HP-NEM as a potential therapeutic agent in breast cancer treatment.
Topics: Apoptosis; Breast Neoplasms; Female; HEK293 Cells; Hesperidin; Humans; MCF-7 Cells; MicroRNAs
PubMed: 34510994
DOI: 10.1080/02652048.2021.1979673 -
International Journal of Environmental... Apr 2022Humans are exposed to residues of organophosphate and neonicotinoid pesticides, commonly used in agriculture. Children are particularly vulnerable and, among possible...
Humans are exposed to residues of organophosphate and neonicotinoid pesticides, commonly used in agriculture. Children are particularly vulnerable and, among possible adverse outcomes, the increased incidence of premature mammary gland development (thelarche) has raised concern. We evaluated the toxicological effects of chlorpyrifos (CPF), imidacloprid (IMI) and glyphosate (GLY) at exposure concentrations occurring in children on the tumorigenic MCF-7 and non-tumorigenic MCF-12A breast cell lines, as representative of the target organ model, assessing cytotoxicity, apoptosis, necrosis, intracellular reactive oxygen species (ROS) and ATP levels, 17β-estradiol secretion and gene expression of nuclear receptors involved in mammary gland development. The pesticides decreased cell vitality in MCF-7 and cell proliferation in MCF-12A cells. ATP levels were decreased in MCF-7 cells by pesticides and apoptosis was increased in MCF-12A cells only by GLY (2.3 nM). ROS production was decreased by pesticides in both cell lines, except IMI (1.6 nM) in MCF-7 cells. Endocrine disrupting activity was highlighted by induction of 17β-estradiol secretion and modulation of the gene expression of estrogen alpha and beta, progesterone, androgen, and aryl hydrocarbon receptors in both cell lines. The use of MCF-7 and MCF-12A cells highlighted dissimilar modes of action of each pesticide at low human relevant concentrations.
Topics: Adenosine Triphosphate; Breast Neoplasms; Child; Estradiol; Female; Humans; MCF-7 Cells; Pesticides; Reactive Oxygen Species
PubMed: 35457321
DOI: 10.3390/ijerph19084453 -
Pakistan Journal of Pharmaceutical... Jul 2023Selenium is a mineral that is essential to human health and is widely recognized for its responsibilities as a powerful anticancer vitamin and antibacterial vitamin....
Selenium is a mineral that is essential to human health and is widely recognized for its responsibilities as a powerful anticancer vitamin and antibacterial vitamin. Selenium also plays a critical part in the production of vitamin D. The purpose of this research was to evaluate the particular effects that selenium nano-particles (SeNPs') had on the infectious agent Staphylococcus aureus as well as the breast cancer cell lines MCF-7 and MDA-MB-231. The proportion of MDA-MB-231 and MCF-7 cells that underwent late apoptosis was dramatically increased by selenium nanoparticles, whereas the number of cells that underwent cell expansion was significantly reduced. There was a wide range of variability in the effects of selenium nanoparticle treatment on cell growth apoptosis, apoptosis rates and patterns of cell cycle arrest. After 2, 4 and 6 hours, researchers found that the development of S. aureus was significantly reduced by selenium nanoparticles at doses of 8.0, 16.0 and 32g/mL. In addition to this, the presence of selenium nanoparticles resulted in a reduced percentage of bacteria that were still alive. According to the findings of the study, there is a need for more research into selenium nanoparticles with the intention of preventing and treating infections caused by S. aureus.
Topics: Humans; Selenium; MCF-7 Cells; Staphylococcus aureus; Vitamins; Vitamin D
PubMed: 37606024
DOI: No ID Found -
Artificial Cells, Nanomedicine, and... Dec 2019The aim of this paper was examining the combined impacts of CuO nanoparticles (CuO NPs), hyperthermia (H), and irradiation (R) on an increment of MCF-7 cells. The MTT...
The aim of this paper was examining the combined impacts of CuO nanoparticles (CuO NPs), hyperthermia (H), and irradiation (R) on an increment of MCF-7 cells. The MTT assay was employed to assess the antiproliferative effects of CuO NPs (25, 50, and 100 μg/ml), hyperthermia (41 °C for 1 h), and irradiation (200 cGy). Moreover, the perniciousness was estimated through the survival capability of cells, and apoptosis, ROS production, and levels of caspase-3, -8 and -9 proteins were determined. A significant (p < .01) decrease in proliferation index (0.124 ± 0.021), a significant (p < .01) increase in apoptosis (42% ± 1.54) of MCF7 cells, a significant (p < .03) increase in ROS formation (32.16 ± 1.9) and a significant (p < .01) increase in LDH release (33.28 ± 1.56) were recorded in the adjacency of MCF-7 cells by a combination of CuO NPs (100 µg/ml) and R + H compared to control and other treatments. The activities of caspase-3 (0.33 ± 0.014) and caspase-9 (0.389 ± 0.019) also increased significantly (p < .05). However, caspase-8 showed no significant changes in its activity (p = .065). Based on these observations, a combination of CuO NPs, hyperthermia, and irradiation could suppress the growth of MCF-7 cells and evoke cell apoptosis via mitochondrial membrane potential.
Topics: Apoptosis; Caspases; Cell Survival; Combined Modality Therapy; Copper; Humans; Hyperthermia, Induced; L-Lactate Dehydrogenase; MCF-7 Cells; Nanoparticles; Radiotherapy; Reactive Oxygen Species
PubMed: 30964344
DOI: 10.1080/21691401.2019.1600529