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Environmental Research Apr 2023Breast and cervical cancer account for the majority of cancer-narrated fatalities among women worldwide, necessitating the development of novel, effective therapeutic...
Breast and cervical cancer account for the majority of cancer-narrated fatalities among women worldwide, necessitating the development of novel, effective therapeutic ways to combat the disease. In this study, we synthesized 6-methoxy naphthalene and anthracene-based acrylamide chalcone (NBA and ABA) and evaluated its activity for cell multiplication inhibition against two cancer cell lines from humans such as MCF-7 (Human Breast) and HeLa (Cervical) by MTT assay. Physiochemical characterization, such as FT-IR and NMR analyses, validated the synthesized NBA and ABA. Both NBA and ABA have shown antiproliferative action against two cancer cell lines, each with IC50 values of 38.46 and 48.25 μg/mL for HeLa cells and 38.02 and 36.35 μg/mL for MCF-7 cell lines. The results suggest that these acrylamide chalcones for cancer therapy at the lowest concentration. NBA and ABA could prevent cervical and breast cancer in-vitro, and their anti-cancer activity was closely related to methoxy-substituted naphthalene, anthracene ring, α, β-unsaturated carbonyl and amide group. According to docking data, the NBA and ABA have dock scores ranging from -8.7 to -11.44 kcal/mol. The highest dock score for compound ABA was -11.58 kcal/mol and compound NBA was -10.77 kcal/mol with Braf (5VAM) binding site.
Topics: Humans; Female; Chalcone; Molecular Structure; Chalcones; Structure-Activity Relationship; MCF-7 Cells; HeLa Cells; Acrylamides; Spectroscopy, Fourier Transform Infrared; Drug Screening Assays, Antitumor; Cell Proliferation; Naphthalenes; Antineoplastic Agents; Cell Line, Tumor; Dose-Response Relationship, Drug; Neoplasms
PubMed: 36731601
DOI: 10.1016/j.envres.2023.115395 -
International Journal of Molecular... Jun 2022Vascular and lymphatic vessels drive breast cancer (BC) growth and metastasis. We assessed the cell growth (proliferation, migration, and capillary formation), gene-,...
Vascular and lymphatic vessels drive breast cancer (BC) growth and metastasis. We assessed the cell growth (proliferation, migration, and capillary formation), gene-, and protein-expression profiles of Vascular Endothelial Cells (VECs) and Lymphatic Endothelial Cells (LECs) exposed to a conditioned medium (CM) from estrogen receptor-positive BC cells (MCF-7) in the presence or absence of Estradiol. We demonstrated that MCF-7-CM stimulated growth and capillary formation in VECs but inhibited LEC growth. Consistently, MCF-7-CM induced ERK1/2 and Akt phosphorylation in VECs and inhibited them in LECs. Gene expression analysis revealed that the LECs were overall (≈10-fold) more sensitive to MCF-7-CM exposure than VECs. Growth/angiogenesis and cell cycle pathways were upregulated in VECs but downregulated in LECs. An angiogenesis proteome array confirmed the upregulation of 23 pro-angiogenesis proteins in VECs. In LECs, the expression of genes related to ATP synthesis and the ATP content were reduced by MCF-7-CM, whereas MTHFD2 gene, involved in folate metabolism and immune evasion, was upregulated. The contrasting effect of MCF-7-CM on the growth of VECs and LECs was reversed by inhibiting the TGF-β signaling pathway. The effect of MCF-7-CM on VEC growth was also reversed by inhibiting the VEGF signaling pathway. In conclusion, BC secretome may facilitate cancer cell survival and tumor growth by simultaneously promoting vascular angiogenesis and inhibiting lymphatic growth. The differential effects of BC secretome on LECs and VECs may be of pathophysiological relevance in BC.
Topics: Adenosine Triphosphate; Breast Neoplasms; Endothelial Cells; Female; Humans; Lymphangiogenesis; MCF-7 Cells; Neovascularization, Pathologic; Secretome; Transcriptome
PubMed: 35806196
DOI: 10.3390/ijms23137192 -
Anti-cancer Agents in Medicinal... 2022Conventional therapies for breast cancer are still a challenge due to cytotoxic drugs not being highly effective with significant adverse effects. Thiohydantoins are...
BACKGROUND
Conventional therapies for breast cancer are still a challenge due to cytotoxic drugs not being highly effective with significant adverse effects. Thiohydantoins are biologically active heterocyclic compounds reported for several biological activities, including anticarcinogenic properties, etc. This work aims to assess the use of thiohydantoin as a potential antitumor agent against MCF-7 breast cancer cells.
METHODS
MTT and neutral red assays were used to assess the possible cytotoxic activity of compounds against MCF-7 cells. Cell volume measurement and analysis were performed by flow cytometry. Fluorescence analysis was carried out to determine patterns of cell death induced by thiohydantoins.
RESULTS
The treatment with micromolar doses of thiohydantoins promoted a decrease in the viability of MCF-7 breast tumor cells. An increase in the ROS and NO production, reduction in cell volume, loss of membrane integrity, mitochondrial depolarization, and increased fluorescence for annexin-V and caspase-3 were also observed. These findings indicate cell death by apoptosis and increased autophagic vacuoles, stopping the cell cycle in the G1/ G0 phase.
CONCLUSION
Our results indicate that thiohydantoins are cytotoxic to breast tumor cells, and this effect is linked to the increase in ROS production. This phenomenon changes tumorigenic pathways, which halt the cell cycle in G1/G0. This is an essential checkpoint for DNA errors, which may have altered how cells produce energy, causing a decrease in mitochondrial viability and thus leading to the apoptotic process. Furthermore, the results indicate increased autophagy, a vital process linked to a decrease in lysosomal viability and thus considered a cell death and tumor suppression mechanism.
Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Humans; MCF-7 Cells; Reactive Oxygen Species; Thiohydantoins
PubMed: 34382528
DOI: 10.2174/1871520621666210811102441 -
Journal of Biomolecular Structure &... Mar 2022This study investigates the molecular mechanisms underlying the anticancer activity of hesperidin and luteolin, isolated from in the human breast carcinoma cell line...
This study investigates the molecular mechanisms underlying the anticancer activity of hesperidin and luteolin, isolated from in the human breast carcinoma cell line (MCF-7). The viability of MCF-7 cells, upon treatment with hesperidin and luteolin, was evaluated using the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay; apoptotic activity and effect on cell cycle progression were analysed by flow cytometry; effect on expression of key apoptotic regulatory genes (caspase-3, -8, -9, and ) and apoptotic microRNAs (-16, -21 and -34a) were evaluated using quantitative real-time PCR. Hesperidin and luteolin reduced cell viability in a dose and time-dependent manner, caused a significant accumulation of apoptotic cells into the G0/G1 and sub-G1 cell cycle phases, induced apoptosis through the intrinsic and extrinsic pathways, down-regulated anti-apoptotic, , and upregulated pro-apoptotic, . In addition, hesperidin and luteolin significantly downregulated the expression of miR-21 and upregulated that of miR-16 and -34a in MCF-7. Spearman`s rank analysis revealed a positive correlation between and miR-21 and negative correlation between , miR-16 and -34a. Findings from this study provide new evidence on the molecular basis of the anticancer activity of luteolin and hesperidin in breast cancer cell lines.Communicated by Ramaswamy H. Sarma.
Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Hesperidin; Humans; Luteolin; MCF-7 Cells; MicroRNAs
PubMed: 33050842
DOI: 10.1080/07391102.2020.1833757 -
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 -
Journal of Photochemistry and... Oct 2022This work reports on the reactive oxygen species (ROS) generation and the therapeutic activities of new triphenyl-phosphonium-labelled phthalocyanines (Pcs), the...
Enhanced mitochondria destruction on MCF-7 and HeLa cell lines in vitro using triphenyl-phosphonium-labelled phthalocyanines in ultrasound-assisted photodynamic therapy activity.
This work reports on the reactive oxygen species (ROS) generation and the therapeutic activities of new triphenyl-phosphonium-labelled phthalocyanines (Pcs), the 2,9,16,23-tetrakis(N-(N-butyl-4-triphenyl-phosphonium)- pyridine-4-yloxy) Zn(II) Pc (3) and 2,9,16,23-tetrakis-(N-(N-butyl-4-triphenyl-phosphonium)-morpholino) Zn(II) Pc (4) upon exposure to light, ultrasound and the combination of light and ultrasound. Two types of ROS were detected: the singlet oxygen (O) and hydroxyl radicals. For light irradiations, only the O was detected. An increase in the ROS generation was observed for samples treated with the combination of light and ultrasound compared to the light and ultrasound mono-treatments. The in vitro anticancer activity through photodynamic (PDT) and sonodynamic (SDT) therapy for the Pcs were also determined and compared to the photo-sonodynamic combination therapy (PSDT). The two cancer cell lines used for the in vitro studies included the Michigan Cancer Foundation-7 (MCF-7) breast cancer and Henrietta Lacks (HeLa) cervical cancer cell lines. The SDT treatments showed improved therapeutic efficacy on the cancer cells for both the Pcs compared to PDT. PSDT showed better therapeutic efficacy compared to both the PDT and SDT mono-treatments.
Topics: Breast Neoplasms; Cell Line, Tumor; Female; HeLa Cells; Humans; Indoles; MCF-7 Cells; Michigan; Mitochondria; Morpholinos; Photochemotherapy; Pyridines; Reactive Oxygen Species; Singlet Oxygen
PubMed: 36084362
DOI: 10.1016/j.jphotobiol.2022.112553 -
Journal of Microencapsulation 2021Hesperidin, a ubiquitous plant-based flavanone, was encapsulated into nanoemulsions (HP-NEM) using a spontaneous emulsification method to improve its solubility and...
Hesperidin, a ubiquitous plant-based flavanone, was encapsulated into nanoemulsions (HP-NEM) using a spontaneous emulsification method to improve its solubility and enhance bioavailability and efficacy in breast cancer treatment using MCF-7 cell lines. The cytotoxic and apoptotic effects of HP-NEM against MCF-7 and its impact on oncomiRs, microRNA-21, and microRNA-155 expression were also assessed. The optimised HP-NEM displayed a spherical shape with 305 ± 40.8 nm, 0.308 ± 0.04, and -11.6 ± 3.30 mV and 93 ± 0.45% for particle size, polydispersity index (PDI), zeta-potential (ζ), and encapsulation efficiency, respectively. Cytotoxicity studies using MTT assay showed selective toxicity of the HP-NEM against MCF-7 without affecting normal cells (HEK 293). Treatment with the HP-NEM induced cell death through apoptosis, cell cycle arrest in the G2/M phase, and downregulated miR-21 and miR-155 expression in MCF-7. This study supports the use of HP-NEM as a potential therapeutic agent in breast cancer treatment.
Topics: Apoptosis; Breast Neoplasms; Female; HEK293 Cells; Hesperidin; Humans; MCF-7 Cells; MicroRNAs
PubMed: 34510994
DOI: 10.1080/02652048.2021.1979673 -
Acta Chimica Slovenica Dec 2022In this study, a series of hydrazide-hydrazone derivatives (3a-3u) were synthesized and evaluated for their anticancer activities against prostate cancer cell line...
In this study, a series of hydrazide-hydrazone derivatives (3a-3u) were synthesized and evaluated for their anticancer activities against prostate cancer cell line (PC-3), breast cancer cell line (MCF-7), colon cancer cell line (HT-29) and human umbilical vein endothelial cells (HUVEC) using MTT assay. In particular, compound 3h having a pyrrole ring was found to be the most potent derivative with IC50 = 1.32, 2.99, 1.71 µM against PC-3, MCF-7, HT-29 cancer cell lines respectively using paclitaxel as a standard compound. Furthermore, compound 3h was subjected to further biological studies such as caspase-3 activity and Annexin-V assay to evaluate their inhibitory potentials. The activity results displayed that compound 3h increased caspase-3 activation and the number of cells to early apoptosis. The additional studies like pharmacokinetics, bioavailability scores and drug-likeness properties were also evaluated. The in silico pharmacokinetics predictions displayed that the bioavailability of these compounds may be high.
Topics: Humans; Hydrazones; Structure-Activity Relationship; Cell Line, Tumor; Hydrazines; Caspase 3; Drug Design; Antineoplastic Agents; Human Umbilical Vein Endothelial Cells; Drug Screening Assays, Antitumor; Cell Proliferation; Molecular Structure; Dose-Response Relationship, Drug
PubMed: 36562164
DOI: 10.17344/acsi.2022.7614 -
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