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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 -
Mathematical Biosciences and... Jul 2019Breast cancer is the second most commonly diagnosed cancer in women worldwide. MCF-7 cell line is an extensively studied human breast cancer cell line. This cell line...
Breast cancer is the second most commonly diagnosed cancer in women worldwide. MCF-7 cell line is an extensively studied human breast cancer cell line. This cell line expresses estrogen receptors, and the growth of MCF-7 cells is hormone dependent. In this study, a mathematical model, which governs MCF-7 cell growth with interaction among tumor cells, estradiol, natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) or CD8+ T cells, and white blood cells (WBCs), is proposed. Experimental data are used to determine functional forms and parameter values. Breast tumor growth is then studied using the mathematical model. The results obtained from numerical simulation are compared with those from clinical and experimental studies. The system has three coexisting stable equilibria representing the tumor free state, a microscopic tumor, and a large tumor. Numerical simulation shows that an immune system is able to eliminate or control a tumor with a restricted initial size. A healthy immune system is able to effectively eliminate a small tumor or produces long-term dormancy. An immune system with WBC count at the low parts of the normal ranges or with temporary low NK cell count is able to eliminate a smaller tumor. The cytotoxicity of CTLs plays an important role in immune surveillance. The association between the circulating estradiol level and cancer risk is not significant.
Topics: Breast Neoplasms; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cell Proliferation; Computer Simulation; Estradiol; Female; Humans; Immune System; Killer Cells, Natural; Leukocytes; MCF-7 Cells; Models, Theoretical; Receptor, ErbB-2; Receptors, Estrogen
PubMed: 31698574
DOI: 10.3934/mbe.2019325 -
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 -
Nature Methods Oct 2023Protein complexes are responsible for the enactment of most cellular functions. For the protein complex to form and function, its subunits often need to be present at...
Protein complexes are responsible for the enactment of most cellular functions. For the protein complex to form and function, its subunits often need to be present at defined quantitative ratios. Typically, global changes in protein complex composition are assessed with experimental approaches that tend to be time consuming. Here, we have developed a computational algorithm for the detection of altered protein complexes based on the systematic assessment of subunit ratios from quantitative proteomic measurements. We applied it to measurements from breast cancer cell lines and patient biopsies and were able to identify strong remodeling of HDAC2 epigenetic complexes in more aggressive forms of cancer. The presented algorithm is available as an R package and enables the inference of changes in protein complex states by extracting functionally relevant information from bottom-up proteomic datasets.
Topics: Humans; Proteome; Proteomics; Algorithms; MCF-7 Cells; Computational Biology
PubMed: 37749212
DOI: 10.1038/s41592-023-02011-w -
Discovery Medicine 2022Glycogen synthase kinase 3 beta (GSK3β) has emerged as a therapeutic target for breast cancer. As inhibitors of GSK-3β, 1,2,4-thiadiazole-3,5-dione (TDZD) family...
Glycogen synthase kinase 3 beta (GSK3β) has emerged as a therapeutic target for breast cancer. As inhibitors of GSK-3β, 1,2,4-thiadiazole-3,5-dione (TDZD) family members have been reported as potential candidates for cancer treatment. In this study, the anticancer effects of ethiadin (ETD-174), one of the chemical synthesis compounds of TDZD, were investigated in MCF-7 human breast cancer cells. MCF-7 cells incubated with different doses of ETD-174 for different time periods. CCK-8 assays were carried out to test the effect of ETD-174 on the proliferation of MCF-7 cells. The occurrence of apoptosis was detected by Hoechst 33258 staining and flow cytometry. ETD-174 on cell migration and colony formation were examined by wound healing experiments and soft agar assays. Relative protein expressions were conducted with immunoblot assay. ETD-174 demonstrated a higher degree of cytotoxicity in MCF-7 cells. Topical morphological changes of apoptotic body formation after ETD-174 treatment were observed. Meanwhile, apoptosis was elicited by ETD-174. Also, ETD-174 could inhibit the migration and clonality of MCF-7 cells. After the treatment with ETD-174, the level of phosphorylation of GSK3β in MCF-7 cells increased significantly, and the enzymatic activity of GSK3β decreased. ETD-174 is likely to have an effective suppressor role in breast cancer, suggesting that pharmacological inhibition of GSK3β as a novel treatment modality for breast cancer should warrant further investigation.
Topics: Humans; Female; MCF-7 Cells; Glycogen Synthase Kinase 3 beta; Breast Neoplasms; Apoptosis
PubMed: 36482736
DOI: No ID Found -
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 -
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 -
International Journal of Oncology Mar 2021Ampelopsis megalophylla has been found to demonstrate anticancer activities in human cancer cells; however, the effect of total flavone extract (TFE), commonly used in...
Ampelopsis megalophylla has been found to demonstrate anticancer activities in human cancer cells; however, the effect of total flavone extract (TFE), commonly used in Traditional Chinese Medicine, remains unclear. Furthermore, there is limited information on its effects on breast cancer cell lines. The present study aimed to investigate the inhibitory effects of TFE in different human cancer cell lines. In addition, the underlying mechanisms and the signaling pathways involved were also investigated by determining tumor cell morphological changes, and differences in the cell cycle, apoptosis, mitochondrial transmembrane potential, and related protein expression levels in a breast cancer cell line. It was found that TFE inhibited proliferation in seven cancer cell lines (HeLa, A549, MCF‑7, HepG2, A2780, SW620 and MDA‑MB‑231 and demonstrated a strong inhibitory effect on MCF‑7 cell proliferation. Cell morphological changes were also observed and arrested at the G2/M phase following treatment with TFE at different concentrations. In addition, TFE disrupted the mitochondrial membrane potential and upregulated the expression level of apoptotic proteins, including caspase‑3, ‑8 and ‑9, the Bax/Bcl‑2 ratio, and Apaf‑1 in time‑dependent manner. These results indicated that TFE induced apoptosis of the MCF‑7 cells via a mitochondrial‑mediated apoptotic pathway. In conclusion, TFE is potentially effective in treating breast cancer.
Topics: Ampelopsis; Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Female; Humans; MCF-7 Cells; Mitochondria; Plant Extracts
PubMed: 33469684
DOI: 10.3892/ijo.2021.5172 -
Cells Nov 2022During disease progression and bone metastasis, breast tumor cells interact with various types of bystander cells residing in the tumor microenvironment. Such...
During disease progression and bone metastasis, breast tumor cells interact with various types of bystander cells residing in the tumor microenvironment. Such interactions prompt tumor cell heterogeneity. We used successive co-culture as an experimental model to examine cancer-bystander cell interaction. RMCF7-2, a clone of the human breast cancer MCF-7 cells tagged with a red fluorescent protein, was tracked for morphologic, behavioral, and gene expression changes. Co-cultured with various types of hematopoietic cells, RMCF7-2 adopted stable changes to a rounded shape in suspension growth of red fluorescent cells, from which derivative clones displayed marked expressional changes of marker proteins, including reduced E-cadherin and estrogen receptor α, and loss of progesterone receptor. In a successive co-culture with bone marrow-derived mesenchymal stem/stromal cells, the red fluorescent clones in suspension growth changed once more, adopting an attachment growth, but in diversified shapes. Red fluorescent clones recovered from the second-round co-culture were heterogeneous in morphology, but retained the altered marker protein expression while displaying increased proliferation, migration, and xenograft tumor formation. Interaction with bystander cells caused permanent morphologic, growth behavioral, and gene expressional changes under successive co-culture, which is a powerful model for studying cancer cell heterogeneity during breast cancer progression and metastasis.
Topics: Humans; Female; MCF-7 Cells; Coculture Techniques; Breast Neoplasms; Bone Marrow; Mesenchymal Stem Cells; Tumor Microenvironment
PubMed: 36428982
DOI: 10.3390/cells11223553 -
International Journal of Molecular... Feb 2022To target breast cancer (BC), epigenetic modulation could be a promising therapy strategy due to its role in the genesis, growth, and metastases of BC. Valproic acid...
To target breast cancer (BC), epigenetic modulation could be a promising therapy strategy due to its role in the genesis, growth, and metastases of BC. Valproic acid (VPA) is a well-known histone deacetylase inhibitor (HDACi), which due to its epigenetic focus needs to be studied in depth to understand the effects it might elicit in BC cells. The aim of this work is to contribute to exploring the complete pharmacological mechanism of VPA in killing cancer cells using MCF-7. LC-MS/MS metabolomics studies were applied to MCF-7 treated with VPA. The results show that VPA promote cell death by altering metabolic pathways principally pentose phosphate pathway (PPP) and 2'deoxy-α-D-ribose-1-phosphate degradation related with metabolites that decrease cell proliferation and cell growth, interfere with energy sources and enhance reactive oxygen species (ROS) levels. We even suggest that mechanisms such as ferropoptosis could be involved due to deregulation of L-cysteine. These results suggest that VPA has different pharmacological mechanisms in killing cancer cells including apoptotic and nonapoptotic mechanisms, and due to the broad impact that HDACis have in cells, metabolomic approaches are a great source of information to generate new insights for this type of molecule.
Topics: Apoptosis; Breast Neoplasms; Chromatography, Liquid; Female; Histone Deacetylase Inhibitors; Humans; MCF-7 Cells; Metabolomics; Tandem Mass Spectrometry; Valproic Acid
PubMed: 35269790
DOI: 10.3390/ijms23052645