-
European Journal of Nutrition Sep 2019Watercress is a rich source of phytochemicals with anticancer potential, including phenethyl isothiocyanate (PEITC). We examined the potential for watercress extracts...
PURPOSE
Watercress is a rich source of phytochemicals with anticancer potential, including phenethyl isothiocyanate (PEITC). We examined the potential for watercress extracts and PEITC to increase the DNA damage caused by ionising radiation (IR) in breast cancer cells and to be protective against radiation-induced collateral damage in healthy breast cells. The metabolic events that mediate such responses were explored using metabolic profiling.
METHODS
H nuclear magnetic resonance spectroscopy-based metabolic profiling was coupled with DNA damage-related assays (cell cycle, Comet assay, viability assays) to profile the comparative effects of watercress and PEITC in MCF-7 breast cancer cells and MCF-10A non-tumorigenic breast cells with and without exposure to IR.
RESULTS
Both the watercress extract and PEITC-modulated biosynthetic pathways of lipid and protein synthesis and resulted in changes in cellular bioenergetics. Disruptions to the redox balance occurred with both treatments in the two cell lines, characterised by shifts in the abundance of glutathione. PEITC enhanced the sensitivity of the breast cancer cells to IR increasing the effectiveness of the cancer-killing process. In contrast, watercress-protected non-tumorigenic breast cells from radiation-induced damage. These effects were driven by changes in the cellular content of the antioxidant glutathione following exposure to PEITC and other phytochemicals in watercress.
CONCLUSION
These findings support the potential prophylactic impact of watercress during radiotherapy. Extracted compounds from watercress and PEITC differentially modulate cellular metabolism collectively enhancing the therapeutic outcomes of radiotherapy.
Topics: Anticarcinogenic Agents; Apoptosis; Cell Line, Tumor; Humans; Isothiocyanates; MCF-7 Cells; Magnetic Resonance Spectroscopy; Nasturtium; Radiation, Ionizing
PubMed: 30066177
DOI: 10.1007/s00394-018-1789-8 -
PloS One 2017Mammalian lignans or enterolignans are metabolites of plant lignans, an important category of phytochemicals. Although they are known to be associated with estrogenic...
Mammalian lignans or enterolignans are metabolites of plant lignans, an important category of phytochemicals. Although they are known to be associated with estrogenic activity, cell signaling pathways leading to specific cell functions, and especially the differences among lignans, have not been explored. We examined the estrogenic activity of enterolignans and their precursor plant lignans and cell signaling pathways for some cell functions, cell cycle and chemokine secretion. We used DNA microarray-based gene expression profiling in human breast cancer MCF-7 cells to examine the similarities, as well as the differences, among enterolignans, enterolactone and enterodiol, and their precursors, matairesinol, pinoresinol and sesamin. The profiles showed moderate to high levels of correlation (R values: 0.44 to 0.81) with that of estrogen (17β-estradiol or E2). Significant correlations were observed among lignans (R values: 0.77 to 0.97), and the correlations were higher for cell functions related to enzymes, signaling, proliferation and transport. All the enterolignans/precursors examined showed activation of the Erk1/2 and PI3K/Akt pathways, indicating the involvement of rapid signaling through the non-genomic estrogen signaling pathway. However, when their effects on specific cell functions, cell cycle progression and chemokine (MCP-1) secretion were examined, positive effects were observed only for enterolactone, suggesting that signals are given in certain directions at a position closer to cell functions. We hypothesized that, while estrogen signaling is initiated by the enterolignans/precursors examined, their signals are differentially and directionally modulated later in the pathways, resulting in the differences at the cell function level.
Topics: 4-Butyrolactone; Cell Cycle; Dioxoles; Estrogens; Furans; Gene Expression Profiling; Humans; Lignans; MCF-7 Cells; Oligonucleotide Array Sequence Analysis; Signal Transduction
PubMed: 28152041
DOI: 10.1371/journal.pone.0171390 -
Oncology Reports Jan 2023Cancer can be fatal if it is not treated in a timely manner; therefore, there is a high demand for more specific oncology drugs. Unfortunately, drugs showing positive...
Cancer can be fatal if it is not treated in a timely manner; therefore, there is a high demand for more specific oncology drugs. Unfortunately, drugs showing positive responses on a two‑dimensional (2D) culture platform do not often show the same effect in clinical trials. Therefore, three‑dimensional (3D) culture platforms are garnering attention since they more closely mimic the tumor microenvironment (TME). The TME stimulates metastasis and drug resistance, and serves an essential role in tumor formation. An accurate understanding of tumor‑stroma interactions is undoubtedly required to improve the response of patients to therapeutic strategies, and cancer therapeutic strategies that do not account for the stroma are considered inadequate. It should be noted that 3D monoculture systems do not completely mimic the TME since other cells in the 3D culture are missing, such as fibroblast or endothelial cells, which are essential components of the stroma; therefore, it is essential to develop advanced 3D culture systems. The present study aimed to develop a versatile triculture model that mimics the native TME; therefore, it could aid in high‑throughput screening of chemotherapeutic drugs against cancer by evaluating their effects on tumor progression and cell cytotoxicity. The present study demonstrated the use of the AXTEX‑4D™ platform in developing triculture tissueoids composed of MCF‑7, human umbilical vein endothelial cells and MRC5 cells, and compared it with a 3D monoculture model (MCF‑7) and a 2D culture model. The triculture model was validated for proliferation, ECM markers and T‑cell infiltration by confocal microscopy. Alamar Blue assay demonstrated that triculture tissueoids exhibited higher drug resistance than the other two models, thus demonstrating their use in the screening of oncology drugs.
Topics: Humans; Tumor Microenvironment; Neoplasms; Fibroblasts; Human Umbilical Vein Endothelial Cells; Cell Line, Tumor
PubMed: 36367183
DOI: 10.3892/or.2022.8439 -
Small (Weinheim An Der Bergstrasse,... Jul 2016To understand the inhomogeneity of cells in biological systems, there is a growing demand on the capability of characterizing the properties of individual single cells....
To understand the inhomogeneity of cells in biological systems, there is a growing demand on the capability of characterizing the properties of individual single cells. Since single-cell studies require continuous monitoring of the cell behaviors, an effective single-cell assay that can support time lapsed studies in a high throughput manner is desired. Most currently available single-cell technologies cannot provide proper environments to sustain cell growth and, proliferation of single cells and convenient, noninvasive tests of single-cell behaviors from molecular markers. Here, a highly versatile single-cell assay is presented that can accommodate different cellular types, enable easy and efficient single-cell loading and culturing, and be suitable for the study of effects of in vitro environmental factors in combination with drug screening. One salient feature of the assay is the noninvasive collection and surveying of single-cell secretions at different time points, producing unprecedented insight of single-cell behaviors based on the biomarker signals from individual cells under given perturbations. Above all, the acquired information is quantitative, for example, measured by the number of exosomes each single-cell secretes for a given time period. Therefore, our single-cell assay provides a convenient, low-cost, and enabling tool for quantitative, time lapsed studies of single-cell properties.
Topics: Cell Line, Tumor; Exosomes; Humans; MCF-7 Cells; Single-Cell Analysis
PubMed: 27254278
DOI: 10.1002/smll.201600725 -
Marine Drugs Feb 2022In this paper, eight new galaxamide analogues (~) were synthesized and evaluated for their cytotoxic activities against five cancer cell lines, MCF-7, MD-MBA-231, HepG2,...
In this paper, eight new galaxamide analogues (~) were synthesized and evaluated for their cytotoxic activities against five cancer cell lines, MCF-7, MD-MBA-231, HepG2, Hela, and A549, using MTT assays. The modified analogue displayed broad spectrum cytotoxic activity toward each tested cell line with IC values of 1.65 ± 0.30 (MCF-7), 2.91 ± 0.17 (HepG2), 4.59 ± 0.27 (MD-MBA-231), 5.69 ± 0.37 (Hela), and 5.96 ± 0.41 (A549) μg/mL, respectively. The galaxamides and induced concentration-dependent apoptosis of the MCF-7 cells after 72 h as evaluated by the flow cytometry experiment. The results showed that these compounds could induce MCF-7 cell apoptosis by arresting the G0/G1 phase of the cell cycle and finally achieving the effect of inhibiting the proliferation of MCF-7 cells.
Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Human Umbilical Vein Endothelial Cells; Humans; Peptides, Cyclic
PubMed: 35323457
DOI: 10.3390/md20030158 -
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 -
Analytical Chemistry Apr 2021Breast cancer is one of the leading causes of cancer death in women. Novel in vitro tools that integrate three-dimensional (3D) tumor models with highly sensitive...
Breast cancer is one of the leading causes of cancer death in women. Novel in vitro tools that integrate three-dimensional (3D) tumor models with highly sensitive chemical reporters can provide useful information to aid biological characterization of cancer phenotype and understanding of drug activity. The combination of surface-enhanced Raman scattering (SERS) techniques with microfluidic technologies offers new opportunities for highly selective, specific, and multiplexed nanoparticle-based assays. Here, we explored the use of functionalized nanoparticles for the detection of estrogen receptor alpha (ERα) expression in a 3D tumor model, using the ERα-positive human breast cancer cell line MCF-7. This approach was used to compare targeted versus nontargeted nanoparticle interactions with the tumor model to better understand whether targeted nanotags are required to efficiently target ERα. Mixtures of targeted anti-ERα antibody-functionalized nanotags (ERα-AuNPs) and nontargeted (against ERα) anti-human epidermal growth factor receptor 2 (HER2) antibody-functionalized nanotags (HER2-AuNPs), with different Raman reporters with a similar SERS signal intensity, were incubated with MCF-7 spheroids in microfluidic devices and spectroscopically analyzed using SERS. MCF-7 cells express high levels of ERα and no detectable levels of HER2. 2D and 3D SERS measurements confirmed the strong targeting effect of ERα-AuNP nanotags to the MCF-7 spheroids in contrast to HER2-AuNPs (63% signal reduction). Moreover, 3D SERS measurements confirmed the differentiation between the targeted and the nontargeted nanotags. Finally, we demonstrated how nanotag uptake by MCF-7 spheroids was affected by the drug fulvestrant, the first-in-class approved selective estrogen receptor degrader (SERD). These results illustrate the potential of using SERS and microfluidics as a powerful in vitro platform for the characterization of 3D tumor models and the investigation of SERD activity.
Topics: Breast Neoplasms; Cell Line, Tumor; Estrogen Receptor alpha; Female; Fulvestrant; Gold; Humans; MCF-7 Cells; Metal Nanoparticles; Microfluidics
PubMed: 33797884
DOI: 10.1021/acs.analchem.1c00188 -
International Journal of Molecular... Dec 2022A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized. An MTT assay revealed that most of tested hybrids showed more enhanced...
A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized. An MTT assay revealed that most of tested hybrids showed more enhanced anti-proliferative activities than artemisinin, among which A8 had the superior potency with IC values ranging from 4.07 μM to 9.71 μM against five tested cancer cell lines. Cell colony formation assays showed that A8 could inhibit significantly more cell proliferation than artemisinin and 5-fluorouracil. Further mechanism studies reveal that A8 induces apoptosis and ferroptosis in MCF-7 cells in a dose-dependent manner, and CYPs inhibition assays reveal that A8 has a moderate inhibitory effect on CYP1A2 and CYP3A4 in the human body at 10 μM. The present work indicates that hybrid A8 may merit further investigation as a potential therapeutic agent.
Topics: Humans; MCF-7 Cells; Molecular Structure; Ferroptosis; Antineoplastic Agents; Drug Screening Assays, Antitumor; Apoptosis; Artemisinins; Cell Proliferation; Structure-Activity Relationship; Cell Line, Tumor
PubMed: 36555409
DOI: 10.3390/ijms232415768 -
ACS Applied Materials & Interfaces May 2019We report new surface coatings that adhesively distinguish three breast epithelial cell lines (MCF-10A, MCF-7, and TMX2-28) when cell suspensions in buffer or breast...
We report new surface coatings that adhesively distinguish three breast epithelial cell lines (MCF-10A, MCF-7, and TMX2-28) when cell suspensions in buffer or breast milk are flowed over the coatings. We also report the selective capture of epithelial cells and rejection of Jurkat lymphocytes, with average selectivities exceeding 60 and captured cell purities often exceeding >99%. The surfaces achieve the dual goals of selective cell capture and resistance to fouling by proteins and other components of breast milk. The coatings do not rely on antibody targeting of cell surface markers but instead contain polycation chains embedded within a layer of end-tethered poly(ethylene glycol) (PEG) chains. The PEG, somewhat shielding the polycations, prevents surface fouling by proteins, nondesired cells, and other milk components, while the polycations produce electrostatic attractions that are heterogeneous on nanoscopic length scales. These electrostatic heterogeneities on the engineered coating, shown to produce curvature-selective particle capture in other studies, produce cell selectivity here. The ability of the engineered surfaces to discriminate these cell lines via an electrostatic driving force is remarkable, as the cells are of very similar surface charge as evidenced by their nearly identical ζ-potentials. The current surfaces, which likely distinguish cells based on their electrostatic surface landscape combined with other factors, adhesively distinguish cell lines that may differ only slightly in their expression of a surface marker, or cancer cells that minimally express EpCAM but which have different distributions of electrostatic charge on their surfaces. These surfaces are among the first to be documented for the compatibility of a polymer brush with human breast milk and may find use in technologies that capture cells from human breast milk or other complex fluids for cancer risk assessment.
Topics: Adhesives; Breast; Buffers; Epithelial Cell Adhesion Molecule; Epithelial Cells; Female; Gene Expression; Humans; Jurkat Cells; Lymphocytes; MCF-7 Cells; Milk, Human; Polyethylene Glycols; Polymers; Surface Properties
PubMed: 31032616
DOI: 10.1021/acsami.9b03385 -
Molecules (Basel, Switzerland) Nov 2023The anticarcinogenic potential of a series of 1,5-disubstituted tetrazole-1,2,3-triazole hybrids (T-THs) was evaluated in the breast cancer (BC)-derived cell lines MCF-7...
The anticarcinogenic potential of a series of 1,5-disubstituted tetrazole-1,2,3-triazole hybrids (T-THs) was evaluated in the breast cancer (BC)-derived cell lines MCF-7 (ER+, PR+, and HER2-), CAMA-1 (ER+, PR+/-, and HER2-), SKBR-3 (ER+, PR+, and HER2+), and HCC1954 (ER+, PR+, and HER2+). The T-THs , , and inhibited the proliferation of MCF-7 and CAMA-1, HCC1954, and SKBR-3 cells, respectively. The compounds with stronger effect in terms of migration and invasion inhibition were , , , and for the CAMA-1, MCF-7, HCC1954, and SKBR-3 cells respectively. Interestingly, these T-THs were the compounds with a fluorine present in their structures. To discover a possible target protein, a molecular docking analysis was performed for p53, p38, p58, and JNK1. The T-THs presented a higher affinity for p53, followed by JNK1, p58, and lastly p38. The best-predicted affinity for p53 showed interactions between the T-THs and both the DNA fragment and the protein. These results provide an opportunity for these compounds to be studied as potential drug candidates for breast cancer treatment.
Topics: Humans; Female; MCF-7 Cells; Breast Neoplasms; Tumor Suppressor Protein p53; Molecular Docking Simulation; Cell Line, Tumor; Triazoles; Cell Proliferation
PubMed: 38005322
DOI: 10.3390/molecules28227600