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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 -
Toxicology and Applied Pharmacology Oct 20221α, 25, dihydroxyvitamin D (1,25D), the active form of vitamin D, has antitumor properties in several cancer cell lines in vitro. Salinomycin (Sal) has anticancer...
1α, 25, dihydroxyvitamin D (1,25D), the active form of vitamin D, has antitumor properties in several cancer cell lines in vitro. Salinomycin (Sal) has anticancer activity against cancer cell lines. This study aims to examine the cytotoxic and antiproliferative effect of Sal associated with 1,25D on MCF-7 breast carcinoma cell line cultured in monolayer (2D) and three-dimensional models (mammospheres). We also aim to evaluate the molecular mechanism of Sal and 1,25D-mediated effects. We report that Sal and 1,25D act synergistically in MCF-7 mammospheres and monolayer causing G1 cell cycle arrest, reduction of mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) overproduction with a long-lasting cytotoxic response represented by clonogenic and mammosphere assay. We observed the induction of cell death by apoptosis with upregulation in mRNA levels of apoptosis-related genes (CASP7, CASP9, and BBC3). Extensive cytoplasmic vacuolization, a morphological characteristic found in paraptosis, was also seen and could be triggered by endoplasmic reticulum stress (ER) as we found transcriptional upregulation of genes related to ER stress (ATF6, GADD153, GADD45G, EIF2AK3, and HSPA5). Overall, Sal and 1,25D act synergistically, inhibiting cell proliferation by activating simultaneously multiple death pathways and may be a novel and promising luminal A breast cancer therapy strategy.
Topics: Antineoplastic Agents; Apoptosis; Cell Culture Techniques, Three Dimensional; Cell Line, Tumor; Cholecalciferol; Endoplasmic Reticulum Stress; Humans; MCF-7 Cells; Pyrans
PubMed: 35914560
DOI: 10.1016/j.taap.2022.116178 -
Biomedicine & Pharmacotherapy =... Jul 2022Tissues are subjected to dynamic communication between cells and the extracellular matrix (ECM), resulting in ECM remodeling. One of the ECM components is elastin, which...
Tissues are subjected to dynamic communication between cells and the extracellular matrix (ECM), resulting in ECM remodeling. One of the ECM components is elastin, which releases elastin-derived peptides (EDPs) during the aging process. Therefore, the aim of the present study was to evaluate the impact of the VGVAPG hexapeptide and elastin-like peptide VVGPGA (control) on certain metabolism parameters in human breast adenocarcinoma (MCF-7) and human lung carcinoma (A549) cell lines. The results did not show a significant effect of the peptides on metabolic activity and caspase-3 activity. However, more specific analysis revealed that VGVAPG and VVGPGA were able to increase KI67 protein expression in both tested cell lines after 24-h treatment. Moreover, the same correlation was observed at the KI67 gene level. VGVAPG also increased the P53, ATM and SHH gene expression in the A549 cells up to 19.08%, 20.74%, and 28.77%, respectively. Interestingly, the VGVAPG peptide exerted an effect on the expression of antioxidant enzymes SOD2 and CAT in the A549 and MCF-7 cells, especially after the 24-h treatment. Lastly, both peptides influenced the CAV1 and CLTC1 expression. Our results show that the tested EDPs have an effect on both A549 and MCF-7 cells at the cellular level. This may be correlated with the multidrug-resistance (MDR) phenotype in these cancer cells, which is an emerging problem in the current anticancer treatment. However, more research is needed in this field.
Topics: A549 Cells; Elastin; Humans; Ki-67 Antigen; Lung; MCF-7 Cells; Neoplasms; Oligopeptides; Peptides
PubMed: 35598370
DOI: 10.1016/j.biopha.2022.113149 -
BioMed Research International 2022Combination of natural products with chemically synthesised biomaterials as cancer therapy has attracted great interest lately. Hence, this study is aimed at...
Combination of Goniothalamin and Sol-Gel-Derived Bioactive Glass 45S5 Enhances Growth Inhibitory Activity Apoptosis Induction and Cell Cycle Arrest in Breast Cancer Cells MCF-7.
BACKGROUND
Combination of natural products with chemically synthesised biomaterials as cancer therapy has attracted great interest lately. Hence, this study is aimed at investigating the combined effects of goniothalamin and bioactive glass 45S5 (GTN-BG) and evaluating their anticancer properties on human breast cancer cells MCF-7.
METHODS
The BG 45S5 was prepared using the sol-gel process followed by characterisation using PSA, BET, SEM/EDS, XRD, and FTIR. The effects of GTN-BG on the proliferation of MCF-7 were assessed by MTT, PrestoBlue, and scratch wound assays. The cell cycle analysis, Annexin-FITC assay, and activation of caspase-3/7, caspase-8, and caspase-9 assays were determined to further explore its mechanism of action.
RESULTS
The synthesised BG 45S5 was classified as a fine powder, having a rough surface, and contains mesopores of 12.6 nm. EDS analysis revealed that silica and calcium elements are the primary components of BG powders. Both crystalline and amorphous structures were detected with 73% and 27% similarity to NaCa(SiO) and hydroxyapatite, respectively. The combination of GTN-BG was more potent than GTN in inhibiting the proliferation of MCF-7 cells. G0/G1 and G2/M phases of the cell cycle were arrested by GTN and GTN-BG. The percentage of viable cells in GTN-BG treatment was significantly lower than that in GTN. In terms of activation of initiator caspases for both extrinsic and intrinsic apoptosis pathways, caspase-8 and caspase-9 were found more effective in response to GTN-BG than GTN.
CONCLUSION
The anticancer effect of GTN in MCF-7 cells was improved when combined with BG. The findings provide significant insight into the mechanism of GTN-BG against MCF-7 cells, which can potentially be used as a novel anticancer therapeutic approach.
Topics: Apoptosis; Breast Neoplasms; Caspase 8; Caspase 9; Cell Cycle Checkpoints; Cell Proliferation; Ceramics; Female; Glass; Humans; MCF-7 Cells; Pyrones
PubMed: 35872839
DOI: 10.1155/2022/5653136 -
Cancer Reports (Hoboken, N.J.) May 2023Cancer stem cells (CSCs), subpopulations of cancer cells, are responsible for tumor progression, metastasis, and relapse. Changes in amino acid metabolism are linked to...
BACKGROUND
Cancer stem cells (CSCs), subpopulations of cancer cells, are responsible for tumor progression, metastasis, and relapse. Changes in amino acid metabolism are linked to breast cancer recurrence and metastasis.
AIMS
This study aimed to evaluate the changes in the amino acid profile in MCF-7 and MDA-MB-231 cells during spheroid formation to discover the specific metabolic properties in CSCs.
METHODS
MCF-7 and MDA-MB-231 breast cancer cells were cultured as spheroids and evaluated to characterize their CSC properties. The characteristics of CSC were evaluated by examining the expression of CSC markers and conducting drug resistance assays. In addition, amino acid profile change during the enrichment of breast cancer stem cells in the spheroids was investigated by high-performance liquid chromatography (HPLC).
RESULTS
The results indicated that out of 20 different amino acids analyzed, 19 of them decreased during the spheroid formation process. Alanine, lysine, phenylalanine, threonine, and glycine showed significant reductions in the conditioned media of both cell lines in the spheroid form compared to the monolayer cells. Only one of the amino acids increased in MCF-7 and MDA-MB-231 spheroids (histidine and serine, respectively).
CONCLUSION
Our results suggest that certain amino acids identified in this study can be used for a better understanding of the molecular mechanisms associated with breast cancer stem cell formation.
Topics: MCF-7 Cells; MDA-MB-231 Cells; Humans; Neoplastic Stem Cells; Spheroids, Cellular; Amino Acids; Chromatography, High Pressure Liquid; Drug Resistance, Neoplasm
PubMed: 37092500
DOI: 10.1002/cnr2.1809 -
Scientific Reports Aug 2023The implication of inflammation in the pathophysiology of several types of cancers has been under intense investigation. Conjugated fatty acids can modulate inflammation...
The implication of inflammation in the pathophysiology of several types of cancers has been under intense investigation. Conjugated fatty acids can modulate inflammation and present anticancer effects, promoting cancer cell death. In this paper, we evaluated the efficacy of new conjugated fatty acids isolated from marine Opisthopterus tardoore (Tapra fish) in human breast cancer cell lines MCF-7. Linoelaidic acid, a marine fish (O. tardoore) derived unsaturated fatty acids, showed effective anticancer activity against MCF-7. Cell viability (MTT) assay revealed a dose-dependent decline in cancer cell viability. It was noteworthy that 5 µM linoelaidic acid decreased the MCF-7 cell viability by 81.82%. Besides that, linoelaidic acid significantly (P< 0.05) increased the level of tumor necrosis factor-α (TNF-α) and interleukin-1 receptor antagonist (IL-1ra) studied by ELISA. Not only that, linoelaidic acid significantly decreased the reduced glutathione level and increased the oxidized glutathione level in MCF-7 cells indicating the oxidative stress inside the cell. Two different cell staining methods with acridine orange-ethidium bromide and DAPI confirmed that the linoelaidic acid rendered their detrimental effect on cancer cells. To decipher the mode of apoptosis Western blotting was performed in which the expression pattern of several proteins (p53, IL-10, and IL-1ra) established the apoptosis in the studied cell lines after linoelaidic acid exposure. Hence it may be conferred that linoelaidic acid has prompt anticancer activity. Therefore this drug can be used further for the treatment of cancer.
Topics: Humans; Linoleic Acid; MCF-7 Cells; Reactive Oxygen Species; Interleukin 1 Receptor Antagonist Protein; Cell Death; Fatty Acids; Dietary Fats, Unsaturated; Caspases
PubMed: 37644076
DOI: 10.1038/s41598-023-34885-3 -
BMC Cancer Nov 2023Breast cancer is the most common malignancy globally, and is considered a major cause of cancer-related death. Tremendous effort is exerted to identify an optimal...
Anti-proliferative activity of RIHMS-Qi-23 against MCF-7 breast cancer cell line is through inhibition of cell proliferation and senescence but not inhibition of targeted kinases.
BACKGROUND
Breast cancer is the most common malignancy globally, and is considered a major cause of cancer-related death. Tremendous effort is exerted to identify an optimal anticancer drug with limited side effects. The quinoline derivative RIMHS-Qi-23 had a wide-spectrum antiproliferative activity against various types of cancer cells.
METHODS
In the current study, the effect of RIMHS-Qi-23 was tested on MCF-7 breast cancer cell line to evaluate its anticancer efficacy in comparison to the reference compound doxorubicin.
RESULTS
Our data suggest an anti-proliferative effect of RIMHS-Qi-23 on the MCF-7 cell line with superior potency and selectivity compared to doxorubicin. Our mechanistic study suggested that the anti-proliferative effect of RIMHS-Qi-23 against MCF-7 cell line is not through targeted kinase inhibition but through other molecular machinery targeting cell proliferation and senescence such as cyclophlin A, p62, and LC3.
CONCLUSION
RIMHS-Qi-23 is exerting an anti-proliferative effect that is more potent and selective than doxorubicin.
Topics: Humans; Female; MCF-7 Cells; Breast Neoplasms; Antineoplastic Agents; Cell Proliferation; Doxorubicin; Cell Line, Tumor
PubMed: 37919708
DOI: 10.1186/s12885-023-11547-1 -
International Journal of Molecular... Apr 2023Korean ginseng is a source of functional foods and medicines; however, its productivity is hindered by abiotic stress factors, such as light. This study investigated the...
Korean ginseng is a source of functional foods and medicines; however, its productivity is hindered by abiotic stress factors, such as light. This study investigated the impacts of darkness and different light wavelengths on the metabolomics and anti-cancer activity of ginseng extracts. Hydroponically-grown Korean ginseng was shifted to a light-emitting diodes (LEDs) chamber for blue-LED and darkness treatments, while white fluorescent (FL) light treatment was the control. MCF-7 breast cancer and lipopolysaccharide (LPS)-induced BV-2 microglial cells were used to determine chemo-preventive and neuroprotective potential. Overall, 53 significant primary metabolites were detected in the treated samples. The levels of ginsenosides Rb1, Rb2, Rc, Rd, and Re, as well as organic and amino acids, were significantly higher in the dark treatment, followed by blue-LED treatment and the FL control. The dark-treated ginseng extract significantly induced apoptotic signaling in MCF-7 cells and dose-dependently inhibited the NF-κB and MAP kinase pathways in LPS-induced BV-2 cells. Short-term dark treatment increased the content of Rd, Rc, Rb1, Rb2, and Re ginsenosides in ginseng extracts, which promoted apoptosis of MCF-7 cells and inhibition of the MAP kinase pathway in BV-2 microglial cells. These results indicate that the dark treatment might be effective in improving the pharmacological potential of ginseng.
Topics: Humans; Ginsenosides; Plant Extracts; Panax; MCF-7 Cells; Darkness; Lipopolysaccharides
PubMed: 37175475
DOI: 10.3390/ijms24097768 -
International Journal of Molecular... Feb 2020The S-Allyl-L-cysteine (SAC) component of aged garlic extract (AGE) is proven to have anticancer, antihepatotoxic, neuroprotective and neurotrophic properties....
The S-Allyl-L-cysteine (SAC) component of aged garlic extract (AGE) is proven to have anticancer, antihepatotoxic, neuroprotective and neurotrophic properties. -Cystathionase (CTH), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (MPST) are involved in HS/sulfane sulfur endogenous formation from L-cysteine. The aim of the study was to determine the effect of SAC on MCF-7 cells survival and apoptosis, which is a widely known approach to reduce the number of cancer cells. An additional goal of this paper was to investigate the effect of SAC on the activity and expression of enzymes involved in HS production. The experiments were carried out in the human breast adenocarcinoma cell line MCF-7. Changes in the cell viability were determined by MTT assay. Cell survival was determined by flow cytometry (FC). Changes in enzymes expression were analyzed using Western blot. After 24 h and 48 h incubation with 2245 µM SAC, induction of late apoptosis was observed. A decrease in cell viability was observed with increasing SAC concentration and incubation time. SAC had no significant cytotoxic effect on the MCF-7 cells upon all analyzed concentrations. CTH, MPST and CBS expression were confirmed in non-treated MCF-7 cells. Significant decrease in MPST activity at 2245 µM SAC after 24 h and 48 h incubation vs. 1000 µM SAC was associated with decrease in sulfane sulfur levels. The presented results show promising SAC effects regarding the deterioration of the MCF-7 cells' condition in reducing their viability through the downregulation of MPST expression and sulfate sulfur level reduction.
Topics: Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cysteine; Humans; Hydrogen Sulfide; MCF-7 Cells; Plant Extracts; Sulfurtransferases
PubMed: 32041330
DOI: 10.3390/ijms21031090 -
Molecules (Basel, Switzerland) Aug 2023We investigated the anticancer mechanism of a chloroform extract of marine sponge () (sample C) in human breast adenocarcinoma (MCF-7) cells. Viability analysis using...
We investigated the anticancer mechanism of a chloroform extract of marine sponge () (sample C) in human breast adenocarcinoma (MCF-7) cells. Viability analysis using MTT and neutral red uptake (NRU) assays showed that sample C exposure decreased the proliferation of cells. Flow cytometric data exhibited reactive oxygen species (ROS), nitric oxide (NO), dysfunction of mitochondrial potential, and apoptosis in sample C-treated MCF-7 cells. A qPCR array of sample C-treated MCF-7 cells showed crosstalk between different pathways of apoptosis, especially , , and genes. Immunofluorescence analysis affirmed the localization of p53, bax, bcl2, MAPKPK2, PARP-1, and caspase-3 proteins in exposed cells. Bioassay-guided fractionation of sample C revealed Neviotin A as the most active compound triggering maximum cell death in MCF-7, indicating its pharmacological potency for the development of a drug for the treatment of human breast cancer.
Topics: Humans; Transcriptome; MCF-7 Cells; Gene Expression Profiling; Cell Death; Apoptosis
PubMed: 37687120
DOI: 10.3390/molecules28176289