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Toxicology in Vitro : An International... Dec 2015(R)-goniothalamin (R-GNT) is a styryl lactone that exhibits antiproliferative property against several tumor cell lines. (S)-goniothalamin (S-GNT) is the synthetic...
(R)-goniothalamin (R-GNT) is a styryl lactone that exhibits antiproliferative property against several tumor cell lines. (S)-goniothalamin (S-GNT) is the synthetic enantiomer of R-GNT, and their biological properties are poorly understood. The aim of this study was to evaluate the antiproliferative mechanisms of (R)-goniothalamin and (S)-goniothalamin in MCF-7 breast cancer cells and HB4a epithelial mammary cells. To determine the mechanisms of cell growth inhibition, we analyzed the ability of R-GNT and S-GNT to induce DNA damage, cell cycle arrest and apoptosis. Moreover, the gene expression of cell cycle components, including cyclin, CDKs and CKIs, as well as of genes involved in apoptosis and the DNA damage response were evaluated. The natural enantiomer R-GNT proved more effective in both cell lines than did the synthetic enantiomer S-GNT, inhibiting cell proliferation via cell cycle arrest and apoptosis induction, likely in response to DNA damage. The cell cycle inhibition caused by R-GNT was mediated through the upregulation of CIP/KIP cyclin-kinase inhibitors and through the downregulation of cyclins and CDKs. S-GNT, in turn, was able to cause G0/G1 cell cycle arrest and DNA damage in MCF-7 cells and apoptosis induction only in HB4a cells. Therefore, goniothalamin presents potent antiproliferative activity to breast cancer cells MCF-7. However, exposure to goniothalamin brings some undesirable effects to non-tumor cells HB4a, including genotoxicity and apoptosis induction.
Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Proliferation; DNA Damage; Female; Humans; MCF-7 Cells; Pyrones; Stereoisomerism
PubMed: 26522230
DOI: 10.1016/j.tiv.2015.10.012 -
Journal of B.U.ON. : Official Journal... 2016This study was designed to explore the effect of colchicine on the proliferation and apoptosis of Breast Cancer Michigan Cancer Foundation - 7 (MCF-7) cells.
PURPOSE
This study was designed to explore the effect of colchicine on the proliferation and apoptosis of Breast Cancer Michigan Cancer Foundation - 7 (MCF-7) cells.
METHODS
The experiment was conducted at the University Laboratory of East Provincial Hospital in April, 2015. The first inhibitory effect of colchicine on breast cancer MCF-7 cells was observed by MTT (3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide) assay, and then the effect of colchicine on apoptosis of breast cancer MCF-7 cells was measured by flow cytometry.
RESULTS
The colchicine's inhibitory effect on breast cancer MCF-7 cells gradually increased with increasing concentration and longer exposure time. Breast cancer MCF-7 cells showed different levels of apoptosis with different colchicine concentrations at 24th, 48th and 72nd hrs, and the apoptosis rate tended to be higher with increasing concentration and prolonged exposure time.
CONCLUSION
All the findings suggest that colchicine is able to inhibit proliferation of breast cancer MCF-7 cells and induce cell apoptosis, and the intensity of the effect was associated with dosage and time.
Topics: Apoptosis; Breast Neoplasms; Cell Proliferation; Colchicine; Female; Humans; MCF-7 Cells
PubMed: 27569074
DOI: No ID Found -
Biomolecules May 2018Currently, breast cancer treatment mostly revolves around radiation therapy and surgical interventions, but often these treatments do not provide satisfactory relief to...
Currently, breast cancer treatment mostly revolves around radiation therapy and surgical interventions, but often these treatments do not provide satisfactory relief to the patients and cause unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in the treatment of human breast cancer cells. In the present study, we tested the effect of FMSP-nanoparticles on human breast cancer cells (MCF-7). We tested different concentrations (1.25, 12.5 and 50 µg/mL) of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, a dose of 1.25 µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5 and 50 µg/mL resulted in significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate that FMSP-nanoparticles induce cell death in MCF-7 cells and may be a potential anti-cancer agent for breast cancer treatment.
Topics: Antineoplastic Agents; Cell Death; Fluorescent Dyes; Humans; MCF-7 Cells; Magnetite Nanoparticles; Polystyrenes
PubMed: 29882888
DOI: 10.3390/biom8020032 -
BMC Cancer Jul 2020IMMUNEPOTENT CRP (ICRP) can be cytotoxic to cancer cell lines. However, its widespread use in cancer patients has been limited by the absence of conclusive data on the...
BACKGROUND
IMMUNEPOTENT CRP (ICRP) can be cytotoxic to cancer cell lines. However, its widespread use in cancer patients has been limited by the absence of conclusive data on the molecular mechanism of its action. Here, we evaluated the mechanism of cell death induced by ICRP in HeLa and MCF-7 cells.
METHODS
Cell death, cell cycle, mitochondrial membrane potential and ROS production were evaluated in HeLa and MCF-7 cell lines after ICRP treatment. Caspase-dependence and ROS-dependence were evaluated using QVD.oph and NAC pre-treatment in cell death analysis. DAMPs release, ER stress (eIF2-α phosphorylation) and autophagosome formation were analyzed as well. Additionally, the role of autophagosomes in cell death induced by ICRP was evaluated using SP-1 pre-treatment in cell death in HeLa and MCF-7 cells.
RESULTS
ICRP induces cell death, reaching CC at 1.25 U/mL and 1.5 U/mL in HeLa and MCF-7 cells, respectively. Loss of mitochondrial membrane potential, ROS production and cell cycle arrest were observed after ICRP CC treatment in both cell lines, inducing the same mechanism, a type of cell death independent of caspases, relying on ROS production. Additionally, ICRP-induced cell death involves features of immunogenic cell death such as P-eIF2α and CRT exposure, as well as, ATP and HMGB1 release. Furthermore, ICRP induces ROS-dependent autophagosome formation that acts as a pro-survival mechanism.
CONCLUSIONS
ICRP induces a non-apoptotic cell death that requires an oxidative stress to take place, involving mitochondrial damage, ROS-dependent autophagosome formation, ER stress and DAMPs' release. These data indicate that ICRP could work together with classic apoptotic inductors to attack cancer cells from different mechanisms, and that ICRP-induced cell death might activate an immune response against cancer cells.
Topics: Alarmins; Animals; Antineoplastic Agents; Apoptosis; Autophagosomes; Cattle; Cell Cycle; Cell Proliferation; HeLa Cells; Humans; MCF-7 Cells; Mitochondria; Neoplasms; Oxidative Stress; Reactive Oxygen Species; Transfer Factor
PubMed: 32660440
DOI: 10.1186/s12885-020-07124-5 -
European Review For Medical and... Apr 2019The aim of this study was to explore the mechanism of miR-98-5p in influencing the malignant proliferation and metastasis capacities of breast cancer cells. (Comparative Study)
Comparative Study
OBJECTIVE
The aim of this study was to explore the mechanism of miR-98-5p in influencing the malignant proliferation and metastasis capacities of breast cancer cells.
PATIENTS AND METHODS
Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression level of miR-98-5p and GRB2-associated-binding protein 2 (Gab2) in breast cancer samples and cells. On-line target gene prediction software and Dual-Luciferase reporter assay were used to predict and verify the target genes of miR-98-5p, respectively. Cell proliferation was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Meanwhile, migration and invasion abilities, as well as the changes of epithelial-mesenchymal transition (EMT) after transfection were detected by transwell assay and Western blot assay, respectively.
RESULTS
Compared with adjacent non-tumor tissues and MCF-10A cells, the expression level of miR-98-5p in tumor tissues and MCF-7 cells was significantly declined, whereas Gab2 was markedly up-regulated. Besides, Gab2 was predicted as a target gene of miR-98-5p. Subsequent experiments indicated that the proliferation, migration, invasion and EMT of MCF-7 cells transfected with miR-98-5p were significantly inhibited. However, up-regulation of Gab2 attenuated the biological function of miR-98-5p on malignant abilities of breast cancer cells.
CONCLUSIONS
We showed that miR-98-5p served as anti-oncogene in breast cancer, which might provide a new therapeutic target for its treatment.
Topics: Adaptor Proteins, Signal Transducing; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Female; GRB2 Adaptor Protein; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; MCF-7 Cells; MicroRNAs; Neoplasm Invasiveness; Neoplasm Metastasis; Up-Regulation
PubMed: 31002135
DOI: 10.26355/eurrev_201904_17562 -
Ecotoxicology and Environmental Safety Mar 2022Atrazine (ATZ) is a widely used herbicide worldwide and is a long-suspected endocrine-disrupting chemical. However, most endocrine-disrupting toxicity studies on ATZ...
Atrazine (ATZ) is a widely used herbicide worldwide and is a long-suspected endocrine-disrupting chemical. However, most endocrine-disrupting toxicity studies on ATZ have been based on animal models and those investigating inner mechanisms have only focused on a few genes. Therefore, the possible link between ATZ and endocrine-disrupting toxicity is still unclear. In this study, multi-omics and molecular biology techniques were used to elucidate the possible molecular mechanisms underlying the effect of ATZ exposure on MCF-7 proliferation at environmentally relevant concentrations. Our study is the first report on ATZ-induced one carbon pool by folate metabolic disorder in MCF-7 cells. A concentration of 1 μM ATZ yielded the highest cell viability and was selected for further mechanistic studies. A total of 34 significantly changed metabolites were identified based on metabolomic analysis, including vitamins, amino acids, fatty acids, and corresponding derivatives. Folate and pyridoxal have potential as biomarkers of ATZ exposure. One carbon pool by folate metabolic pathway was identified based on metabolic pathway analysis of the significantly altered pathways. Moreover, FTCD and MTHFD related to this pathway were further identified based on transcriptomic analysis and protein assays. Folate and different forms of 5,6,7,8-tetrahydrofolate, which participate in purine synthesis and associate with methyl groups (SOPC, arachidonic acid, and L-tryptophan) in one carbon pool by the folate metabolic pathway, potentially promote MCF-7 cell proliferation. These findings on the key metabolites and regulation of the related differentially expressed genes in folate metabolism will shed light on the mechanism of MCF-7 cell proliferation after ATZ exposure. Overall, this study provides new insights into the mechanistic understanding of toxicity caused by endocrine-disrupting chemicals.
Topics: Animals; Atrazine; Biomarkers; Herbicides; Humans; MCF-7 Cells; Metabolomics; Transcriptome
PubMed: 35093817
DOI: 10.1016/j.ecoenv.2022.113244 -
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 -
Asian Pacific Journal of Cancer... 2012Discovery of anticancer drugs that kill or disable tumor cells in the presence of normal cells without undue toxicity is a potential challenge for therapeutic care....
Discovery of anticancer drugs that kill or disable tumor cells in the presence of normal cells without undue toxicity is a potential challenge for therapeutic care. Several papers in the literature have emphasized the potential implications of marine products such as seaweeds which exhibit antitumor activity. Study attempts to screen the antitumor effect of Sargassum sp, against chosen cell lines such as MCF-7 (Breast cancer) and Hep-2 (Liver Cancer). Ethanol extract of Sargassum sp. was concentrated using a Soxhlet apparatus and dissolved in DMSO. In vitro cytotoxic activity of Sargassum sp at various concentrations (100 μg/ml-300 μg/ml) screened for antitumor effect against the chosen cell lines using MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole). The study documented that the percentage of cell viability has been reduced with increased concentration, as evidenced by cell death. Sargassum sp extract shows potential cytotoxic activity (P≤0.05) with IC50 of 200 μ g/ml and 250 μg/ml against Hep-2 and MCF-7 cell lines respectively. The ethanol fraction of Sargassum sp induced cell shrinkage, cell membrane blebbing and formation of apoptotic bodies with evidence of bioactive components as profound influencing factors for anti-tumor effects. Further research need to be explored for the successful application of Sargassum sp as a potent therapeutic tool against cancer.
Topics: Cell Line, Tumor; Cell Survival; Humans; MCF-7 Cells; Plant Extracts; Sargassum; Seaweed; Vegetables
PubMed: 23464406
DOI: 10.7314/apjcp.2012.13.12.6073 -
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 -
BMC Complementary Medicine and Therapies Jun 2024Breast cancer is the most common type of cancer diagnosed in women. Finding novel therapeutic agents with significant cytotoxic action and minimal adverse impact on...
In-vitro study of cytotoxic and apoptotic potential of Thalassia hemprichii (Ehren.) Asch. And Enhalus acoroides (L.f.) Royle against human breast cancer cell line (MCF-7) with correlation to their chemical profile.
BACKGROUND
Breast cancer is the most common type of cancer diagnosed in women. Finding novel therapeutic agents with significant cytotoxic action and minimal adverse impact on normal cells becomes crucial. Today, natural anticancer agents present an unconventional method of treating cancer, either as a curative or preventative agent, with considerable concern for marine organisms.
METHODS
The anticancer effect of the alcoholic extract of different Red Sea Seagrasses on MCF-7 human breast cancer cell line has been investigated. Seagrasses were collected from Wadi El Gamal, Red Sea and extracted. Qualitative HPLC analysis was performed on the extracts for the identification of their active biomarkers. This study was aimed to explore the cytotoxic impact of Thalassia hemprichii (Ehren.) and Enhalus acoroides (L.f.) Royle on MCF-7 and their mode of action. Their anti-proliferative effects on cancer cells were performed using Neutral red assay. On the other hand, their apoptotic effect and their capacity to induce cell cycle arrest were investigated by flow cytometry assay. The effect of Seagrasses on the mitochondrial membrane potential (ΔψM) was studied by using JC-1 mitochondrial membrane potential assay kit in Seagrasses treated cancer cells to Δψ Caspases 3/7activity was examined using the colorimetric method. Gene expression analysis and quantitative real time RT-PCR for the sea grasses on MCF-7 was performed. Immune-blotting technique for Bcl-2 and p53 was investigated.
RESULTS
HPLC analysis demonstrated that the extracts contained mainly flavonoids and polyphenols such as Caffeic acid, Chlorogenic acids, catechin and kaempferol that might be responsible for these anticancer effects. Seagrasses alcoholic crude extract markedly suppressed the growth and expansion of MCF-7 cells concentration-dependently with no toxicity against normal human skin fibroblast HSF. Thalassia hemprichii and Enhalus acoroides trigger mode of cell death primarily via apoptosis as confirmed by the flow cytometry. Additionally, they have ability to induce G0/S cell cycle arrest in MCF-7. The data showed the depletion in mitochondrial membrane potential (ΔψM) in the treated cells dose-dependently Caspases 3/7activities markedly increased following 24 h treatment. Finally, Gene expression analysis showed a marked reduction in Bcl-2, Survivin and CDC2 gene expression levels and a significant increase in the expression of p53 and CC2D1A as compared to control cells.
CONCLUSION
In summary, the Methanolic extract of seagrass, Thalassia hemperchii and Enhalus ocoroides are able to induce concentration-dependent cytotoxic effects in human MCF-7 cells through intrinsic pathway of apoptosis in MCF-7 cells. This study reveals the beneficial importance of sea grasses as a source of anticancer agents. Further in vivo study is recommended for the active isolated biomolecules.
Topics: Humans; MCF-7 Cells; Apoptosis; Breast Neoplasms; Female; Plant Extracts; Hydrocharitaceae; Cell Proliferation; Antineoplastic Agents
PubMed: 38915036
DOI: 10.1186/s12906-024-04512-3