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Scientific Reports May 2021The knowledge of cell mechanics is required to understand cellular processes and functions, such as the movement of cells, and the development of tissue engineering in...
The knowledge of cell mechanics is required to understand cellular processes and functions, such as the movement of cells, and the development of tissue engineering in cancer therapy. Cell mechanical properties depend on a variety of factors, such as cellular environments, and may also rely on external factors, such as the ambient temperature. The impact of temperature on cell mechanics is not clearly understood. To explore the effect of temperature on cell mechanics, we employed magnetic tweezers to apply a force of 1 nN to 4.5 µm superparamagnetic beads. The beads were coated with fibronectin and coupled to human epithelial breast cancer cells, in particular MCF-7 and MDA-MB-231 cells. Cells were measured in a temperature range between 25 and 45 °C. The creep response of both cell types followed a weak power law. At all temperatures, the MDA-MB-231 cells were pronouncedly softer compared to the MCF-7 cells, whereas their fluidity was increased. However, with increasing temperature, the cells became significantly softer and more fluid. Since mechanical properties are manifested in the cell's cytoskeletal structure and the paramagnetic beads are coupled through cell surface receptors linked to cytoskeletal structures, such as actin and myosin filaments as well as microtubules, the cells were probed with pharmacological drugs impacting the actin filament polymerization, such as Latrunculin A, the myosin filaments, such as Blebbistatin, and the microtubules, such as Demecolcine, during the magnetic tweezer measurements in the specific temperature range. Irrespective of pharmacological interventions, the creep response of cells followed a weak power law at all temperatures. Inhibition of the actin polymerization resulted in increased softness in both cell types and decreased fluidity exclusively in MDA-MB-231 cells. Blebbistatin had an effect on the compliance of MDA-MB-231 cells at lower temperatures, which was minor on the compliance MCF-7 cells. Microtubule inhibition affected the fluidity of MCF-7 cells but did not have a significant effect on the compliance of MCF-7 and MDA-MB-231 cells. In summary, with increasing temperature, the cells became significant softer with specific differences between the investigated drugs and cell lines.
Topics: Actins; Biomechanical Phenomena; Breast Neoplasms; Bridged Bicyclo Compounds, Heterocyclic; Cell Line, Tumor; Demecolcine; Female; Fibronectins; Heterocyclic Compounds, 4 or More Rings; Humans; MCF-7 Cells; Magnetic Iron Oxide Nanoparticles; Microtubules; Temperature; Thiazolidines
PubMed: 34031462
DOI: 10.1038/s41598-021-90173-y -
Dipeptidyl-Aminopeptidases 8 and 9 Regulate Autophagy and Tamoxifen Response in Breast Cancer Cells.Cells Aug 2023The cytosolic dipeptidyl-aminopeptidases 8 (DPP8) and 9 (DPP9) belong to the DPPIV serine proteases with the unique characteristic of cleaving off a dipeptide...
The cytosolic dipeptidyl-aminopeptidases 8 (DPP8) and 9 (DPP9) belong to the DPPIV serine proteases with the unique characteristic of cleaving off a dipeptide post-proline from the -termini of substrates. To study the role of DPP8 and DPP9 in breast cancer, MCF-7 cells (luminal A-type breast cancer) and MDA.MB-231 cells (basal-like breast cancer) were used. The inhibition of DPP8/9 by 1G244 increased the number of lysosomes in both cell lines. This phenotype was more pronounced in MCF-7 cells, in which we observed a separation of autophagosomes and lysosomes in the cytosol upon DPP8/9 inhibition. Likewise, the shRNA-mediated knockdown of either DPP8 or DPP9 induced autophagy and increased lysosomes. DPP8/9 inhibition as well as the knockdown of the DPPs reduced the cell survival and proliferation of MCF-7 cells. Additional treatment of MCF-7 cells with tamoxifen, a selective estrogen receptor modulator (SERM) used to treat patients with luminal breast tumors, further decreased survival and proliferation, as well as increased cell death. In summary, both DPP8 and DPP9 activities confine macroautophagy in breast cancer cells. Thus, their inhibition or knockdown reduces cell viability and sensitizes luminal breast cancer cells to tamoxifen treatment.
Topics: Humans; Tamoxifen; Autophagy; Macroautophagy; MCF-7 Cells; Aminopeptidases; Neoplasms
PubMed: 37626841
DOI: 10.3390/cells12162031 -
Biomolecules Dec 2020Cervical cancer is among the leading causes of death in women. Chemotherapy options available for cervical cancer include highly cytotoxic drugs such as taxol,...
Cervical cancer is among the leading causes of death in women. Chemotherapy options available for cervical cancer include highly cytotoxic drugs such as taxol, cisplatin, 5-florouracil, and doxorubicin, which are not specific. In the current study, we have identified a new peptide conjugate (Fur-2-Nal-Ala-Phe-CONH) (conjugate ), from screening of a small library of tripeptide-conjugates of furan, as highly potent anticancer compound against human cervical cancer cells (HeLa cells) (IC = 0.15 ± 0.05 µg/mL or 0.28 +/- 0.09 µM). Peptides were constructed on Rink amide resin from - to -terminus followed by capping by α-furoic acid moiety. The synthesized peptides were purified by recycling RP-HPLC, and structures of all the peptides were confirmed by using FABMS/ESIMS, H- NMR, C-NMR, and HR-FABMS. Conjugate was furthermore found to be specifically active against human cervical cancer cells since it did not inhibit the proliferation of other human normal cells (HUVEC (human umbilical vein endothelial cells) and IMR-90 (normal human fibroblasts)), and cancer cells tested (HUVEC, MCF-7, and MDA-MB-231 cells), as well as in mice 3T3 cells (normal fibroblasts). This study revealed a good structure activity relationship of various peptide conjugates. Conjugate in branched forms ( and ) were also synthesized and evaluated against HeLa cells, and results revealed that both were inactive. Atomic force microscopy (AFM) studies and staining with rhodamine 123 and propidium iodide (PI) revealed that conjugate possesses a membranolytic effect and causes the loss of mitochondrial membrane potential.
Topics: 3T3 Cells; Amides; Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Doxorubicin; Drug Screening Assays, Antitumor; Endothelial Cells; Female; Furans; HeLa Cells; Human Umbilical Vein Endothelial Cells; Humans; Inhibitory Concentration 50; MCF-7 Cells; Magnetic Resonance Spectroscopy; Mice; Microscopy, Atomic Force; Peptides; Protein Domains; Uterine Cervical Neoplasms
PubMed: 33339257
DOI: 10.3390/biom10121684 -
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 -
International Journal of Molecular... Aug 2022Pharmacological inhibition of the enzyme activity targeting carbonic anhydrases (CAs) demonstrated antiglaucoma and anticancer effects through pH control. Recently, we...
Pharmacological inhibition of the enzyme activity targeting carbonic anhydrases (CAs) demonstrated antiglaucoma and anticancer effects through pH control. Recently, we reported a series of indole-based benzenesulfonamides as potent CA inhibitors. The present study aimed to evaluate the antitumor effects of these compounds against various cancer cell lines, including breast cancer (MDA-MB-231, MCF-7, and SK-BR-3), lung cancer (A549), and pancreatic cancer (Panc1) cells. Overall, more potent cytotoxicity was observed on MCF-7 and SK-BR-3 cells than on lung or pancreatic cancer cells. Among the 15 compounds tested, and exhibited potent cytotoxic and antimigratory activities against MCF-7 and SK-BR-3 cells in the CoCl-induced hypoxic condition. While and markedly reduced the viability of control siRNA-treated cells, these compounds could not significantly reduce the viability of CA IX-knockdown cells, suggesting the role of CA IX in their anticancer activities. To assess whether these compounds exerted synergism with a conventional anticancer drug doxorubicin (DOX), the cytotoxic effects of or combined with DOX were analyzed using Chou-Talalay and Bliss independence methods. Our data revealed that both and significantly enhanced the anticancer activity of DOX. Among the tested pairs, the combination of DOX with showed the strongest synergism on SK-BR-3 cells. Moreover, this combination further attenuated cell migration compared to the respective drug. Collectively, our results demonstrated that and suppressed tumor growth and cell migration of MCF-7 and SK-BR-3 cells through inhibition of CA IX, and the combination of these compounds with DOX exhibited synergistic cytotoxic effects on these breast cancer cells. Therefore, and may serve as potential anticancer agents alone or in combination with DOX against breast cancer.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Doxorubicin; Drug Synergism; Female; Humans; Indoles; MCF-7 Cells; Pancreatic Neoplasms
PubMed: 36077298
DOI: 10.3390/ijms23179903 -
Archives of Razi Institute 2021Conventional cancer treatments are costly and have different serious side effects for patients. Natural herbal treatments are widely accepted among people because of...
Conventional cancer treatments are costly and have different serious side effects for patients. Natural herbal treatments are widely accepted among people because of their minimal side effects, although there is little scientific knowledge about them. One of these remedies utilizes the root of that has been used for years in Iran to treat different chronic genital diseases. The current study examined the effects of methanolic and ethanolic extracts of (induction of necrosis and apoptosis) on breast cancer (MCF-7), ovarian cancer (A2780), and human cervix cancer (HeLa) cell lines in comparison with normal breast cells. These effects were determined to be morphological alterations in cell light microscopy, by flow cytometry (staining with annexin V and propidium iodide), and by measuring live cells and inhibition concentrations by MTT assay. IC50 of on the MCF-7 cell line (methanolic extract) was 400 µg/ml and for A2780 was 250 µg/ml. The IC50 amount of on the MCF-7 cell line (ethanolic extract) was 750 µg/ml and 1500 for A2780. Results demonstrated that apoptosis and necrosis occurred in MCF-7 and A2780 following the addition of ethanolic and methanolic extracts of to the medium. These findings confirmed the anti-cancer effects of mehthanolic extracts of root and its safety for normal cells; thus, it can be applied in cancer therapy as a novel medication.
Topics: Cell Line, Tumor; Female; HeLa Cells; Humans; MCF-7 Cells; Ovarian Neoplasms; Plant Extracts
PubMed: 34824753
DOI: 10.22092/ari.2020.351952.1545 -
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 -
Scientific Reports Aug 2017Tumour cell migration has an important impact on tumour metastasis. Magnetic manipulation is an ascendant method for guiding and patterning cells. Here, a unique...
Tumour cell migration has an important impact on tumour metastasis. Magnetic manipulation is an ascendant method for guiding and patterning cells. Here, a unique miniaturized microfluidic chip integrating cell isolation and migration assay was designed to isolate and investigate cell migration. The chip was fabricated and composed of a magnet adapter, a polytetrafluoroethylene(PDMS) microfluidic chip and six magnetic rings. This device was used to isolate MCF-7 cells from MDA-MB-231-RFP cells and evaluate the effects of TGF-β on MCF-7 cells. First, the two cell types were mixed and incubated with magnetic beads modified with an anti-EpCAM antibody. Then, they were slowly introduced into the chip. MCF-7 cells bond to the magnetic beads in a ring-shaped pattern, while MDA-MB-231-RFP cells were washed away by PBS. Cell viability was examined during culturing in the micro-channel. The effects of TGF-β on MCF-7 cells were evaluated by migration distance and protein expression. The integrated method presented here is novel, low-cost and easy for performing cell isolation and migration assay. The method could be beneficial for developing microfluidic device applications for cancer metastasis research and could provide a new method for biological experimentation.
Topics: Cell Movement; Epithelial Cells; Female; Humans; Immunomagnetic Separation; MCF-7 Cells; Microfluidics; Transforming Growth Factor beta
PubMed: 28827722
DOI: 10.1038/s41598-017-08661-z -
European Review For Medical and... Oct 2021To explore the biological function of long non-coding RNA (lncRNA) MORT in the malignant progression of breast cancer (BCa) and the underlying mechanism, and to provide...
OBJECTIVE
To explore the biological function of long non-coding RNA (lncRNA) MORT in the malignant progression of breast cancer (BCa) and the underlying mechanism, and to provide a novel strategy for clinical treatment.
PATIENTS AND METHODS
Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect differential level of MORT in BCa specimens and cell lines. The correlation between MORT level and pathological indexes of BCa patients was analyzed. After intervening MORT level in SKBR-3 and MCF-7 cells, cell viability, migratory rate and wound closure were examined through Cell Counting Kit-8 (CCK-8), transwell and wound healing assay, respectively. Dual-Luciferase reporter assay and rescue experiments were conducted to uncover the regulatory effect of MORT on its target gene FGF1. In vivo function of MORT in mediating tumor growth of BCa was finally assessed by generating a xenograft model in nude mice.
RESULTS
MORT was downregulated in BCa tissues and cell lines. Low level of MORT predicted higher rate of distant metastasis in BCa patients. Overexpression of MORT in SKBR-3 cells reduced proliferative and migratory rates, while knockdown of MORT in MCF-7 enhanced them. Moreover, in vivo overexpression of MORT slowed down tumor growth of BCa in nude mice. MORT could negatively regulate its target gene FGF1, which was responsible for the anti-cancer role of MORT in BCa progression.
CONCLUSIONS
MORT is downregulated in BCa specimens, which suppresses proliferative and migratory potentials of BCa cells by negatively regulating FGF1. MORT can be an effective target for precision treatment of BCa.
Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Disease Progression; Female; Fibroblast Growth Factor 1; Gene Knockdown Techniques; HEK293 Cells; Humans; MCF-7 Cells; Mice; Mice, Nude; RNA, Long Noncoding; Xenograft Model Antitumor Assays
PubMed: 34730198
DOI: 10.26355/eurrev_202110_26988 -
PloS One 2022Zingiber ottensii, is widely used in Asian traditional remedies for the treatment of many diseases. The present study explores anticancer activity of Z. ottensii...
Zingiber ottensii, is widely used in Asian traditional remedies for the treatment of many diseases. The present study explores anticancer activity of Z. ottensii essential oil (ZOEO) and its nanoformulations. ZOEO obtained from hydrodistillation of Z. ottensii fresh rhizomes was analysis using gas chromatography mass spectroscopy. Zerumbone (25.21%) was the major compound of ZOEO followed by sabinene (23.35%) and terpene-4-ol (15.97%). Four types of ZOEO loaded nanoformulations; nanoemulsion, microemulsion, nanoemulgels, and microemulgel, were developed. The average droplet size of the nanoemulsion and microemulsion was significantly smaller than that of the nanoemulgel and microemulgel. Comparison with other essential oils of plants of the same family on anticancer activity against A549, MCF-7, HeLa, and K562, ZOEO showed the highest cytotoxicity with IC50 of 43.37±6.69, 9.77±1.61, 23.25±7.73, and 60.49±9.41 μg/mL, respectively. Investigation using flow cytometry showed that ZOEO significantly increased the sub-G1 populations (cell death) in cell cycle analysis and induced cell apoptosis by apoptotic analysis. The developed nanoformulations significantly enhanced cytotoxicity of ZOEO, particularly against MCF-7 with the IC50 of 3.08±2.58, 0.74±0.45, 2.31±0.91, and 6.45±5.84 μg/mL, respectively. Among the four nanoformulations developed in the present study, nanoemulsion and microemulsion were superior to nanoemulgel and microemulgel in delivering ZOEO into cancer cells.
Topics: A549 Cells; Antineoplastic Agents; Cell Line, Tumor; Emulsions; Flow Cytometry; HeLa Cells; Humans; MCF-7 Cells; Nanoparticle Drug Delivery System; Oils, Volatile; Plant Extracts; Plant Oils; Zingiberaceae
PubMed: 35073347
DOI: 10.1371/journal.pone.0262335