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Cellular and Molecular Biology... Sep 2018Melatonin is a hormone of the pineal gland that has a wide range of biological effects such as antioxidant, anti-inflammatory, and anti-tumor activity. Previous studies...
Melatonin is a hormone of the pineal gland that has a wide range of biological effects such as antioxidant, anti-inflammatory, and anti-tumor activity. Previous studies have shown that melatonin also affects survival, proliferation, and apoptosis of the cells. In this study, we investigated the effect of melatonin on apoptosis, self-renewal, and differentiation. For this purpose, MCF-7 and HEK293 cells were subjected to melatonin treatment. Expression of genes related to apoptosis (Bax and Bcl2) and self-renewal and differentiation (Oct4, Sox2, and Nanog) analyzed after the sorting of cancer stem cells from MCF-7 cells. Results showed that the effect of melatonin is dependent on the melatonin concentration and treatment periods. Melatonin treatment decreased the cell proliferation rate of MCF-7 in contrast to HEK293. Also, this treatment increased apoptosis in MCF-7 cells and decreased in HEK293 cells. Gene expression of Nanog was decreased and Sox2 was increased in both cell groups after the melatonin treatment. Expression of Oct4 was decreased in MCF-7 cells and increased in HEK293 cells. We determined that melatonin decreases apoptosis and differentiation of stem cells in normal HEK293 stem cells, but increases apoptosis and differentiation in the MCF-7 cancer stem cells.
Topics: Apoptosis; Blotting, Western; Cell Differentiation; Flow Cytometry; HEK293 Cells; Humans; MCF-7 Cells; Melatonin; Neoplastic Stem Cells
PubMed: 30301504
DOI: No ID Found -
Molecules (Basel, Switzerland) Aug 2023Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of...
Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of their anti-proliferative properties is of great pharmacological interest. Some 2-alkyl-4-amino-thieno[2,3-]pyrimidines - were synthesized, and their cyto- and phototoxicity against BALB 3T3 cells were established by an in vitro 3T3 NRU test. The obtained results indicate that the tested compounds are not cytotoxic or phototoxic, and that they are appropriate to be studied for their anti-proliferative and anti-tumor properties. The anti-proliferative potential of the compounds was investigated on MCF-7 and MDA-MB-231 cancer cells, as well as a MCF-10A cell line (normal human mammary epithelial cells). The most toxic to MCF-7 was thienopyrimidine with IC 13.42 μg/mL (IC 0.045 μM), followed by compound (IC 28.89 μg/mL or IC 0.11 μM). The thienopyrimidine revealed higher selectivity to MCF-7 and lower activity (IC 367 μg/mL i.e., 1.4 μM) than compound with MCF-10A cells. With respect to MDA-MB-231 cells, ester manifested the highest effect with IC 52.56 μg/mL (IC 0.16 μM), and 2-ethyl derivative revealed IC 62.86 μg/mL (IC 0.24 μM). It was estimated that the effect of the substances on the cell cycle progression was due to cell cycle arrest in the G2 stage for MDA-MB-231, while arrest in G1 was detected for the estrogen (ER)-positive MCF-7 cell line. The tested compound's effects on the change of the zeta potential in the tumorigenic cells utilized in this study were determined. The calculation which we performed of the physicochemical properties and pharmacokinetic parameters influencing the biological activity suggested high intestinal absorption, as well as drug-likeness.
Topics: Animals; Mice; Humans; Estrogens; BALB 3T3 Cells; Carboxylic Acids; Carcinogenesis; Dermatitis, Phototoxic; MCF-7 Cells
PubMed: 37687177
DOI: 10.3390/molecules28176347 -
Marine Drugs May 2018A new sesquiterpenoid 9,10-diolhinokiic acid () and a new diterpenoid roussoellol C (), together with 4 known compounds, were isolated from the extracts of laboratory...
A new sesquiterpenoid 9,10-diolhinokiic acid () and a new diterpenoid roussoellol C (), together with 4 known compounds, were isolated from the extracts of laboratory cultures of marine-derived fungus . 9,10-diolhinokiic acid is the first thujopsene-type sesquiterpenoid containing a 9,10-diol moiety, and roussoellol C possesses a novel tetracyclic fusicoccane framework with an unexpected hydroxyl at C-4. These new structures were confirmed by spectroscopic data, chemical method, NMR data calculations and electronic circular dichroism (ECD) calculations. The selected compounds were evaluated for cytotoxicities against five human cancer cell lines, including SW480, HL-60, A549, MCF-7, and SMMC-7721 and the IC values of compound against MCF-7 and against HL-60 cells were 6.5 and 7.9 μM, respectively.
Topics: A549 Cells; Cell Line, Tumor; HL-60 Cells; Humans; MCF-7 Cells; Sesquiterpenes; Talaromyces; Terpenes
PubMed: 29724060
DOI: 10.3390/md16050150 -
Oxidative Medicine and Cellular... 2021Heterocycles containing thienopyrimidine moieties have attracted attention due to their interesting biological and pharmacological activities. In this research article,...
Heterocycles containing thienopyrimidine moieties have attracted attention due to their interesting biological and pharmacological activities. In this research article, we reported the synthesis of a series of new hybrid molecules through merging the structural features of chalcones and pyridothienopyrimidinones. Our results indicated that the synthesis of chalcone-thienopyrimidine derivatives from the corresponding thienopyrimidine and chalcones proceeded in a relatively short reaction time with good yields and high purity. Most of these novel compounds exhibited moderate to robust cytotoxicity against HepG2 and MCF-7 cancer cells similar to that of 5-fluorouracil (5-FU). The results indicated that IC of the two compounds ( and ) showed more potent anticancer activities against HepG2 and MCF-7 than 5-FU. An MTT assay and flow cytometry showed that only and had anticancer activity and antiproliferative activities at the G1 phase against MCF-7 cells, while six compounds (- and ) had cytotoxicity and cell cycle arrest at different phases against HepG2 cells. Their cytotoxicity was achieved through downregulation of Bcl-2 and upregulation of Bax, caspase-3, and caspase-9. Although all tested compounds increased oxidative stress increment of MDA levels and decrement of glutathione reductase (GR) activities compared to control, the , , and in HepG2 and and in MCF-7 achieved the target results. Moreover, there was a positive correlation between cytotoxic efficacy of the compound and apoptosis in both HepG2 ( = 0.531; = 0.001) and MCF-7 ( = 0.219; = 0.349) cell lines. The results of molecular docking analysis of into the binding groove of Bcl-2 revealed relatively moderate binding free energies compared to the selective Bcl-2 inhibitor, DRO. Like venetoclax, compounds showed 2 violations from Lipinski's rule. However, the results of the ADME study also revealed higher drug-likeness scores for compounds than for venetoclax. In conclusion, the tested newly synthesized chalcone-pyridothienopyrimidinone derivatives showed promising antiproliferative and apoptotic effects. Mechanistically, the compounds increased ROS production with concomitant cell cycle arrest and apoptosis. Therefore, regulation of the cell cycle and apoptosis are possible targets for anticancer therapy. The tested compounds could be potent anticancer agents to be tested in future clinical trials after extensive pharmacodynamic, pharmacokinetic, and toxicity profile investigations.
Topics: Apoptosis; Cell Line, Tumor; Chalcones; Hep G2 Cells; Humans; MCF-7 Cells; Molecular Docking Simulation; Molecular Structure; Pyrimidines
PubMed: 35003514
DOI: 10.1155/2021/4759821 -
Artificial Cells, Nanomedicine, and... Dec 2023In order to load metformin in a nano formula and evaluate the produced nano form towards cancer cells, metformin was loaded on natural carrier coconut oil. The formed...
In order to load metformin in a nano formula and evaluate the produced nano form towards cancer cells, metformin was loaded on natural carrier coconut oil. The formed metformin-loaded coconut oil nanoemulsion was characterized by Zeta potential, particle size, drug content, drug release, and drug stability. The formed nanoemulsion was evaluated towards MCF-7, HepG2, and HCT-116 cell lines. Cell cycle analysis and apoptosis mechanism were studied. The nanoemulsion was created using deionized water, 1.5% Span 20, 1.5% Tween 80, 1.5% coconut oil, and 0.5% Metformin in an ultrasonicator to produce a homogenous solution. The anticancer activities of the metformin-loaded coconut nanoemulsion were highly improved compared to non-formulated metformin with IC50s of 8.3 ± 0.1 µg/ml, 12 ± 1.5 µg/ml, 2.685 ± 0.3 µg/ml for MCF-7, HepG2, and HCT-116 cell lines, respectively. There was a 76.5 ± 2.3 and 78.3 ± 3.2% increase in the number of apoptotic cells of MCF-7 and HepG2 cells after nanoemulsion treatment. This formula may be considered a new anticancer medication.
Topics: Humans; Coconut Oil; HCT116 Cells; MCF-7 Cells; Apoptosis; Cocos; Metformin
PubMed: 37589599
DOI: 10.1080/21691401.2023.2246145 -
Molecules (Basel, Switzerland) Feb 2022Three-dimensional cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions. The surface...
Three-dimensional cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions. The surface hydrophobicity strongly influences the promotion of cell aggregate formation. In particular, for spheroid formation, highly water-repellent coatings seem to be required for the significant effects of the process. In this work, surfaces at different wettability have been compared to observe their influence on the growth and promotion of aggregates of representative mammalian cell lines, both tumoral and non-tumoral (3T3, HaCat and MCF-7 cell lines). The effect of increased hydrophobicity from TCPS to agarose hydrogel to mixed organic-inorganic superhydrophobic (SH) coating has been investigated by optical and fluorescence microscopy, and by 3D confocal profilometry, in a time scale of 24 h. The results show the role of less wettable substrates in inducing the formation of spheroid-like cell aggregates at a higher degree of sphericity for the studied cell lines.
Topics: 3T3 Cells; Animals; Cell Culture Techniques; Cell Proliferation; Humans; Hydrogels; Hydrophobic and Hydrophilic Interactions; MCF-7 Cells; Mice; Spheroids, Cellular
PubMed: 35209035
DOI: 10.3390/molecules27041247 -
Journal of Cancer Research and... 2021Medical halophytes plants are potent sources of bioactive secondary metabolite components used against different diseases. Avicenniamarina one of the typical halophytes...
PURPOSE
Medical halophytes plants are potent sources of bioactive secondary metabolite components used against different diseases. Avicenniamarina one of the typical halophytes plant species used in folk medicine to treat smallpox, rheumatism, and ulcer. Despite the richness of A.marina with polyphenolic, flavonoids, terpenoid, and terpene, contents remain poorly investigated against cancer types. Consequently, to explore the function-composition relationship of A.marina hexane leaves crude extract, the current study designed to investigate the cytotoxicity, apoptotic and antiproliferative impacts on the colon (HCT-116), liver (HepG2), and breast (MCF-7) cancer cell lines.
MATERIALS AND METHODS
Therefore, the cytotoxicity impact screening carried out by Sulforhodamine-B assay. While, the initiation of the apoptosis evaluated by chromatin condensing, early apoptosis, late apoptosis and the formation and appearance of apoptotic bodies. On the other hand, the flow cytometry used to identify the phase of inhibition where the determined IC value used. While, the chemical composition of the hexane extract was detected using liquid chromatography-mass spectrometry/mass spectrometry.
RESULTS
Revealed that hexane extract showed a weak induction of apoptosis despite the formation of apoptotic bodies and the high cell inhibitory effect on all tested cell lines with IC values (23.7 ± 0.7, 44.9 ± 0.93, 79.55 ± 0.57) μg/ml on HCT-116, HepG2, and MCF-7, respectively. Furthermore, it showed the ability to inhibit cell cycle in G0/G1 for HCT-116, S phase for HepG2, and MCF-7.
CONCLUSION
In the light of these results, the current study suggests that A.marina leaves hexane extract may be considered as a candidate for further anticancer drug development investigations.
Topics: Apoptosis; Avicennia; Cell Cycle; Cell Proliferation; HCT116 Cells; Hep G2 Cells; Humans; MCF-7 Cells; Neoplasms; Plant Extracts; Plant Leaves
PubMed: 34528536
DOI: 10.4103/jcrt.JCRT_659_19 -
Biochimie Dec 2021It is becoming increasingly evident that mesenchymal stem/stromal cells are recruited by cancer cells from nearby endogenous host stroma and promote events such as tumor...
It is becoming increasingly evident that mesenchymal stem/stromal cells are recruited by cancer cells from nearby endogenous host stroma and promote events such as tumor proliferation, angiogenesis, invasion, and metastasis, as well as mediate therapeutic resistance. Consequently, understanding the regulatory mechanisms of ASCs that influence the tumor microenvironment may provide an avenue for further treatment. To understand the role of the ASC secretome in breast cancer cell proliferation, death, and phenotype alteration, adipose-derived stem cell-conditioned medium (mASC) was used to cultivate MCF-7 and MDA-MB-231 cells. These breast cancer cells in mASC showed a shorter doubling time, higher frequency of EdU positivity, and higher levels of phosphorylated histone 3. In addition, increased expression of cyclin B1 was observed, suggesting that proliferation was induced. The mASC was also able to increase apoptosis in MCF-7 cells, which was confirmed by caspase-7 activation. The number of tumor-initiating cells (CD44 CD24) and migration capacity were increased in cells cultivated in mASC. These data collectively suggest that ASC-conditioned medium can induce selective pressure by increasing cell proliferation, giving rise to a more aggressive phenotype in MCF-7 and MDA-MB-231 cells. Our study provides a foundation for further elucidation of the precise mechanism underlying ASCs in breast cancer cells and the modulation of ASCs in potential therapeutic uses.
Topics: Adipose Tissue; Breast Neoplasms; Cell Differentiation; Cell Proliferation; Coculture Techniques; Female; Humans; MCF-7 Cells; Mesenchymal Stem Cells; Secretome; Tumor Microenvironment
PubMed: 34454978
DOI: 10.1016/j.biochi.2021.08.010 -
Fundamental & Clinical Pharmacology Dec 2022The goal of this work was to see how melatonin affected Bax and Bcl-2 expression, as well as apoptosis and autophagy, in MCF-7 and MDA-MB-231 breast cancer cell lines,...
The goal of this work was to see how melatonin affected Bax and Bcl-2 expression, as well as apoptosis and autophagy, in MCF-7 and MDA-MB-231 breast cancer cell lines, which have distinct hormonal sensitivities. In this study, to investigate the IC50 value of melatonin, varied melatonin concentrations were administered to MCF-7 and MDA-MB-231 breast cancer cell lines. Moreover, cytotoxic activities were analyzed through MTT analysis. Five subgroups were created for both cell lines: control, IC50-MeL, hIC50-MeL, DMSO1, and DMSO2. To evaluate the apoptotic effect of melatonin, immunofluorescence staining methods of TUNEL, Bax, and Bcl-2 were used, and to examine the effects of autophagy, immunofluorescence staining methods of Beclin-1, LC3, and p62 were used. In vitro results revealed upregulation of the expression of TUNEL and Bax in both MCF-7 and MDA-MB-231 cell lines regarding dose and time, but downregulation of Bcl-2 expression. Moreover, autophagy results were consistent with in vitro apoptosis results in both MCF-7 and MDA-MB-231 cell lines. We determined that the expressions of the autophagy markers Beclin-1, LC3, and p62 were increased. Our findings indicate that treatment of breast cancer cells with melatonin increased the inhibitory effect of melatonin on cell growth through both apoptosis and autophagy in vitro. Consequently, it was concluded that melatonin might adjust the expression balance of markers that have a role in cell death mechanisms and significantly promote these mechanisms. Therefore, melatonin can inhibit the growth of breast cancer cells by inducing cell death.
Topics: Humans; Female; MCF-7 Cells; Melatonin; Beclin-1; bcl-2-Associated X Protein; Breast Neoplasms; Apoptosis; Autophagy; Cell Proliferation; Cell Line, Tumor
PubMed: 35778975
DOI: 10.1111/fcp.12813 -
Monoclonal Antibodies in... Oct 2023The erythropoietin-producing hepatocellular carcinoma (Eph) receptors are the largest receptor tyrosine kinase family. EphB4 is essential for cell adhesion and motility...
The erythropoietin-producing hepatocellular carcinoma (Eph) receptors are the largest receptor tyrosine kinase family. EphB4 is essential for cell adhesion and motility during embryogenesis. Pathologically, EphB4 is overexpressed and contributes to poor prognosis in various tumors. Therefore, specific monoclonal antibodies (mAbs) should be developed to predict the prognosis for multiple tumors with high EphB4 expression, including breast and gastric cancers. This study aimed to develop specific anti-EphB4 mAbs for multiple applications using the Cell-Based Immunization and Screening method. EphB4-overexpressed Chinese hamster ovary (CHO)-K1 (CHO/EphB4) cells were immunized into mice, and we established an anti-EphB4 mAb (clone B4Mab-7), which is applicable for flow cytometry, Western blot, and immunohistochemistry (IHC). B4Mab-7 reacted with endogenous EphB4-positive breast cancer cell line, MCF-7, but did not react with EphB4-knockout MCF-7 (BINDS-52) in flow cytometry. Dissociation constant () values were determined to be 2.9 × 10 M and 1.3 × 10 M by flow cytometric analysis for CHO/EphB4 and MCF-7 cells, respectively. B4Mab-7 detected the EphB4 protein bands from breast cancer cells in Western blot, and stained breast cancer tissues in IHC. Altogether, B4Mab-7 is very useful for detecting EphB4 in various applications.
Topics: Humans; Cricetinae; Animals; Mice; Antibodies, Monoclonal; CHO Cells; Cricetulus; Immunohistochemistry; MCF-7 Cells; Neoplasms
PubMed: 37824755
DOI: 10.1089/mab.2023.0015