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Carbohydrate Research Sep 2022In our previous research on Vietnamese medicinal plants, we found that the ethanolic extract of the aerial parts of Paris polyphylla var. chinensis exhibited cytotoxic...
In our previous research on Vietnamese medicinal plants, we found that the ethanolic extract of the aerial parts of Paris polyphylla var. chinensis exhibited cytotoxic effects in vitro in the MCF-7 human cancer cell line. Here, we used combined chromatographic separations to isolate six compounds including a new steroid glycoside, paripoloside A (3), and five known compounds, from the butanol extract of the aerial parts of P. polyphylla. We unambiguously elucidated their structures based on spectroscopic data (proton and carbon-13 nuclear magnetic resonance, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, correlation spectroscopy, and high-resolution electrospray ionization mass spectroscopy data), and chemical reactions. Among the isolated compounds, paris saponin II (PSII) had the strongest cytotoxic effects against MCF-7 breast cancer cells. Interestingly, PSII significantly increased the expression of p53, p21, p27, and Bax protein levels and significantly suppressed the expression of cyclin D1 and retinoblastoma protein. These data suggest that PSII may induce G1/S phase cell cycle arrest and apoptosis pathway development in MCF-7 cells. Furthermore, the MCF-7 breast cancer cells mechanism of PSII was also investigated using molecular docking. Together, our results demonstrate that isolated compounds from P. polyphylla are promising candidates as breast cancer inhibitors.
Topics: Breast Neoplasms; Cell Cycle Checkpoints; Diosgenin; Female; Humans; Liliaceae; MCF-7 Cells; Molecular Docking Simulation; Plant Components, Aerial; Plant Extracts; Saponins
PubMed: 35752103
DOI: 10.1016/j.carres.2022.108613 -
Analytical Biochemistry Apr 2024Recent studies have revealed the role of endogenous hydrogen sulfide (HS) in the development of breast cancer. The capacity of cells to generate HS and the activity and...
Recent studies have revealed the role of endogenous hydrogen sulfide (HS) in the development of breast cancer. The capacity of cells to generate HS and the activity and expression of the main enzymes (cystathionine beta synthase; CBS, cystathionase γ-lyase; CGL, 3-mercaptopyruvate sulfurtransferase; MPST and thiosulfate sulfurtransferase; TST) involved in HS metabolism were analyzed using an in vitro model of a non-tumourigenic breast cell line (MCF-12A) and a human breast adenocarcinoma cell line (MCF-7). In both cell lines, MPST, CGL, and TST expression was confirmed at the mRNA (RT-PCR) and the protein (Western Blot) level, while CBS expression was detected only in MCF-7 cells. Elevated levels of GSH, sulfane sulfur and increased CBS and TST activity were presented in the MCF-7 compared to the MCF-12A cells. It appears that cysteine might be mainly a substrate for GSH synthesis in breast adenocarcinoma. Increased capacity of the cells to generate HS was shown for MCF-12A compared to MCF-7 cell line. Results suggest an important function of CBS in HS metabolism in breast adenocarcinoma. The presented work may contribute to further research on new therapeutic possibilities for breast cancer - one of the most frequently diagnosed types of cancer among women.
Topics: Humans; Female; MCF-7 Cells; Hydrogen Sulfide; Cystathionine beta-Synthase; Adenocarcinoma; Breast Neoplasms
PubMed: 38141799
DOI: 10.1016/j.ab.2023.115434 -
Pharmacology 2023Worldwide, breast cancer is the most common cancer in women and is the main cause of death among all neoplasia in this group. Luminal A breast cancer represents...
The Aryl Hydrocarbon Receptor Ligand 6-Formylindolo(3,2-b)carbazole Promotes Estrogen Receptor Alpha and c-Fos Protein Degradation and Inhibits MCF-7 Cell Proliferation and Migration.
INTRODUCTION
Worldwide, breast cancer is the most common cancer in women and is the main cause of death among all neoplasia in this group. Luminal A breast cancer represents approximately 70% of all breast cancers and is treated with hormone therapies targeting estrogen receptor alpha (ERα). Unfortunately, patients develop drug resistance leading to recurrence of neoplasia due to estrogen-independent ERα reactivation. Therefore, it is crucial to identify new molecular targets downstream ERα signaling pathway that allows the implementation of better treatments to improve the outcome of breast cancer patients. Overexpression of c-Fos, an ERα gene target, has been associated with increased cell motility, malignancy, metastasis, and invasion while its neutralization results in decreased breast cancer tumorigenesis. The aryl hydrocarbon receptor (AHR) ligands halogenated and polycyclic aromatic hydrocarbons, highly toxic compounds, down regulate c-Fos and ERα levels. The present study aimed to evaluate whether 6-formylindolo(3,2-b)carbazole (FICZ), a no toxic AHR agonist, modifies c-Fos levels in MCF-7 mammary carcinoma cells as well as to determine its effects on cell proliferation and migration. In addition, the possible mechanism through which FICZ mediates c-Fos levels in MCF-7 cells was investigated.
METHODS
Initially, the effect of FICZ on c-Fos mRNA and protein levels in MCF-7 cells, untreated or treated with estradiol, was evaluated by qPCR and Western blot. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin, an AHR prototype agonist, was used as a positive control. Next, we examined the effect of FICZ on MCF-7 cell proliferation and migration by cell counting, MTT, 3H-thymidine incorporation, and scratch-wound assays. Finally, the involvement of proteasome 26S on ERα and c-Fos protein degradation was investigated by the use of MG132 and Western blot.
RESULTS
The data show that FICZ treatment downregulates c-Fos mRNA and protein levels, most likely by promoting ERα proteasome degradation, blocking MCF-7 cell proliferation and migration. The results also demonstrate that liganded ERα was required for FICZ-mediated ERα degradation.
CONCLUSIONS
Activation of AHR results in a decreased MCF-7 cell proliferation and migration by ERα and c-Fos down regulation. Targeting AHR might be a promising therapy for breast cancer treatment, particularly when estrogen-independent ERα reactivation presents.
Topics: Humans; Female; Receptors, Aryl Hydrocarbon; MCF-7 Cells; Estrogen Receptor alpha; Proteasome Endopeptidase Complex; Ligands; Proteolysis; Breast Neoplasms; Estrogens; Cell Proliferation; RNA, Messenger
PubMed: 36657432
DOI: 10.1159/000527993 -
Current Pharmaceutical Design 2022To develop new anticancer agents based on ferrocene core.
New Ferrocene Formates Bearing Isoxazole Moieties: Synthesis, Characterization, X-ray Crystallography, and Preliminarily Cytotoxicity against A549, HCT116, and MCF-7 Cell Lines.
AIMS
To develop new anticancer agents based on ferrocene core.
BACKGROUND
Cancer has become the major cause of human death globally. The death caused by cancer mainly focuses on lung cancer, breast cancer, liver cancer, carcinoma of the colon, and rectum. Some small molecular inhibitors have been authorized by FDA for the treatment of cancer and several candidates are in different phases of clinical trials. However, cancer chemotherapy is still highly inadequate. Thus, it is indispensable to develop novel anticancer agents.
OBJECTIVE
Based on the previous good results, twelve novel structures of ferrocene formates bearing isoxazole moiety (3a-3l) were synthesized in this work for the development of anticancer agents.
METHODS
The target compounds were synthesized using Ferrocenecarboxylic acid and 3-[(R)-substitutedphenyl]- isoxazole-5-methanol catalyzed by DCC and DMAP. The structures of target compounds were characterized by H NMR, C NMR, MS, HR-MS and XRD. Then, their preliminarily in vitro cytotoxicity against A549, HCT116, and MCF-7 cell lines was evaluated using the MTT method.
RESULTS
The results showed that most compounds exhibited moderate cytotoxicity against A549, HCT116, and MCF-7 cell lines compared with the positive control gefitinib. However, (3b, 3c, 3e, 3j, and 3k) simultaneously exhibited stronger inhibitory activity against A549, HCT116, and MCF-7 cell lines, which can be regarded as promising metal-based lead compounds for the development of anticancer agents.
CONCLUSION
In this work, twelve new structures of ferrocene derivatives containing isozaole moiety were synthesized and their cytotoxicity against 549, HCT116, and MCF-7 cell lines was evaluated. (3b, 3c, 3e, 3j, and 3k) simultaneously exhibited stronger inhibitory activity towards A549, HCT116, and MCF-7 cell lines, which can be regarded as promising metal-based lead compounds for the development of anticancer agents.
Topics: Humans; MCF-7 Cells; Metallocenes; Isoxazoles; Crystallography, X-Ray; Formates; Structure-Activity Relationship; Antineoplastic Agents; Drug Screening Assays, Antitumor; Cell Proliferation; Molecular Structure; Cell Line, Tumor
PubMed: 35996233
DOI: 10.2174/1381612828666220822113738 -
Journal of Biological Physics Sep 2021The treatment outcome of a given fractionated radiotherapy scheme is affected by oxygen tension and cell cycle kinetics of the tumor population. Numerous experimental...
The treatment outcome of a given fractionated radiotherapy scheme is affected by oxygen tension and cell cycle kinetics of the tumor population. Numerous experimental studies have supported the variability of radiosensitivity with cell cycle phase. Oxygen modulates the radiosensitivity through hypoxia-inducible factor (HIF) stabilization and oxygen fixation hypothesis (OFH) mechanism. In this study, an existing mathematical model describing cell cycle kinetics was modified to include the oxygen-dependent G1/S transition rate and radiation inactivation rate. The radiation inactivation rate used was derived from the linear-quadratic (LQ) model with dependence on oxygen enhancement ratio (OER), while the oxygen-dependent correction for the G1/S phase transition was obtained from numerically solving the ODE system of cyclin D-HIF dynamics at different oxygen tensions. The corresponding cell cycle phase fractions of aerated MCF-7 tumor population, and the resulting growth curve obtained from numerically solving the developed mathematical model were found to be comparable to experimental data. Two breast radiotherapy fractionation schemes were investigated using the mathematical model. Results show that hypoxia causes the tumor to be more predominated by the tumor subpopulation in the G1 phase and decrease the fractional contribution of the more radioresistant tumor cells in the S phase. However, the advantage provided by hypoxia in terms of cell cycle phase distribution is largely offset by the radioresistance developed through OFH. The delayed proliferation caused by severe hypoxia slightly improves the radiotherapy efficacy compared to that with mild hypoxia for a high overall treatment duration as demonstrated in the 40-Gy fractionation scheme.
Topics: Cell Cycle; Computer Simulation; Dose Fractionation, Radiation; Humans; Hypoxia; Kinetics; MCF-7 Cells
PubMed: 34533654
DOI: 10.1007/s10867-021-09580-x -
Chinese Journal of Integrative Medicine Sep 2021To examine the role of carvacrol in modulating PI3K/AKT signaling involved in human breast cancer pathogenesis using in vitro experimental model MCF-7 cells.
OBJECTIVE
To examine the role of carvacrol in modulating PI3K/AKT signaling involved in human breast cancer pathogenesis using in vitro experimental model MCF-7 cells.
METHODS
MTT and lactate dehydrogenase assays were performed with cells treated with different doses of carvacrol (0-250 p mol/L) at different time points (24 and 48 h). The nuclear morphology was assessed in MCF-7 cells with propidium iodide (PI) and acridine orange/ethidium bromide (AO/EB) staining and analyzed by fluorescence microscopy. Events like cell cycle arrest, apoptosis was observed by flow cytometric analysis and expressions of p-Rb, cyclin D1, cyclin-dependent kinase 4 (CDK4), CDK6, Bax, Bcl-2, PI3K/p-AKT was analyzed by immunoblot.
RESULTS
Carvacrol significantly reduced cell viability with the half maximal inhibitory concentration value of 200 µmol/L at 24 and 48 h (P<0.05). importantly, there was a significant increase in the accumulation of the G/G phase upon treatment with carvacrol in MCF-7 cells (P<0.05 or P<0.01). A remarkable decrease in protein expressions of p-Rb, cyclin D1, CDK4 and CDK6 denotes cell cycle arrest (P<0.05 or P<0.01). In addition, carvacrol treatment significantly inhibited PI3K/p-AKT protein expressions leading to induction of apoptosis mediated by decreased Bcl2 and increased Bax protein expressions. Further, Annexin V/PI staining by FACS analysis, dual staining by AO/EB and PI staining studies suggests induction of apoptosis by carvacrol through PI3K/Akt signaling pathway in MCF-7 cells.
CONCLUSION
Carvacrol significantly inhibited the breast cancer MCF-7 cell proliferation and induced apoptosis via suppressing PI3/AKT signaling pathway.
Topics: Apoptosis; Breast Neoplasms; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cymenes; Female; Humans; MCF-7 Cells; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction
PubMed: 32572774
DOI: 10.1007/s11655-020-3193-5 -
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 -
Biomedicine & Pharmacotherapy =... Sep 2017We have recently shown that olmesartan could induce toxicity in HeLa and MCF-7 cell lines. In this study we investigated toxicity mechanism of olmesartan in HeLa and...
We have recently shown that olmesartan could induce toxicity in HeLa and MCF-7 cell lines. In this study we investigated toxicity mechanism of olmesartan in HeLa and MCF-7 cell lines. HeLa and MCF-7 cells were cultured in DMEM in optimum conditions. Cells were pretreated with rutin as an antioxidant and treated with olmesartan as a cytotoxic agent. Cell proliferation was determined by MTT assay. The role of ROS was determined using DCFH-DA by flow cytometry analysis. Also, cells were treated with olmesartan (5mM) and Bay 11-7-82 (25μM) for 24h, then expression of apoptotic proteins including Bax, caspase3 and IκB were investigated in both cell lines by western blotting. Cell viability decreased with olmesartan in malignant cell lines. Kinetic of ROS assay showed increment of ROS generation starting at 2h which peaked at 4h after treatment. Pretreatment with antioxidant rutin decreased ROS increment which was consistent with improved viability of olmesartan-treated cells. Apoptosis results showed that olmesartan and Bay 11-7082 increased expression of apoptotic proteins such as Bax, caspase3 and IκB. Results proposed ROS increment and apoptosis could be involving mechanisms in olmesartan-induced toxicity in HeLa and MCF-7 cell lines.
Topics: Apoptosis; Cell Survival; HeLa Cells; Humans; Imidazoles; Intracellular Space; MCF-7 Cells; NF-kappa B; Nitriles; Protective Agents; Reactive Oxygen Species; Rutin; Signal Transduction; Sulfones; Tetrazoles
PubMed: 28666209
DOI: 10.1016/j.biopha.2017.06.074 -
Chemistry & Biodiversity Jan 2023Breast cancer is known as the most common type of invasive cancer in women. It is well-known that phenolic compounds play an important role in the treatment of this...
Breast cancer is known as the most common type of invasive cancer in women. It is well-known that phenolic compounds play an important role in the treatment of this disease. This study hypothesized that isoeugenol based two polyphenolic compounds 1 and 2 exerts its anti-proliferative effects through the induction of apoptosis and cell migration arrest on human breast cancer cell. Based on this hypothesis, the study aimed to investigate the anti-proliferative, anti-migrative effects of these compounds and their possible basic molecular mechanisms of action in MCF-7 cell lines. As a result, isoeugenol-based compounds 1 and 2 showed anti-proliferative, anti-apoptotic and anti-migrative effects in MCF-7 breast cancer cells. This result was supported by molecular analyzes and it was determined that there were changes in the expression of some gene regions involved in apoptosis and migration. Additionally, it was a remarkable result that cell viability inhibition did not occur in healthy breast tissue cells and no cytotoxic effect was observed. The existence of such a differentiation between cancer cells and healthy cells significantly increases the potential of these compounds to be used as chemotherapeutic drug active ingredients without side effects.
Topics: Humans; Female; MCF-7 Cells; Breast Neoplasms; Cell Proliferation; Polyphenols; Early Detection of Cancer; Antineoplastic Agents; Apoptosis; Cell Line, Tumor
PubMed: 36594615
DOI: 10.1002/cbdv.202200872 -
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