scholarly journals Diversity of the Senescence Phenotype of Cancer Cells Treated with Chemotherapeutic Agents

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1501 ◽  
Author(s):  
Agnieszka Bojko ◽  
Joanna Czarnecka-Herok ◽  
Agata Charzynska ◽  
Michal Dabrowski ◽  
Ewa Sikora
Keyword(s):  
Dna Damage ◽  
Comparative Analysis ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Double Stranded Dna ◽  
Secretory Phenotype ◽  
Paclitaxel Treatment ◽  
Senescence Phenotype ◽  
Mcf 7 ◽  
Intermediate Effect

It is acknowledged that cancer cells are able to undergo senescence in response to clinically used chemotherapeutics. Moreover, recent years have provided evidence that some drugs can selectively remove senescent cells. Therefore, it is essential to properly identify and characterize senescent cells, especially when it comes to cancer. Senescence was induced in various cancer cell lines (A549, SH-SY-5Y, HCT116, MDA-MB-231, and MCF-7) following treatment with doxorubicin, irinotecan, methotrexate, 5-fluorouracil, oxaliplatin, or paclitaxel. Treatment with tested chemotherapeutics resulted in upregulation of p21 and proliferation arrest without cytotoxicity. A comparative analysis with the use of common senescence markers (i.e., morphology, SA-β-galactosidase, granularity, secretory phenotype, and the level of double-stranded DNA damage) revealed a large diversity in response to the chemotherapeutics used. The strongest senescence inducers were doxorubicin, irinotecan, and methotrexate; paclitaxel had an intermediate effect and oxaliplatin and 5-fluorouracil did not induce senescence. In addition, different susceptibility of cancer cells to senescence was observed. A statistical analysis aimed at finding any relationship between the senescence markers applied did not show clear correlations. Moreover, increased SA-β-gal activity coupled with p21 expression proved not to be an unequivocal senescence marker. This points to a need to simultaneously analyze multiple markers, given their individual limitations.

DENSpm overcame Bcl-2 mediated resistance against Paclitaxel treatment in MCF-7 breast cancer cells via activating polyamine catabolic machinery

2016 ◽  
Vol 84 ◽  
pp. 2029-2041 ◽  
Author(s):  
Zeynep Akyol ◽  
Ajda Çoker-Gürkan ◽  
Elif Damla Arisan ◽  
Pınar Obakan-Yerlikaya ◽  
Narçin Palavan-Ünsal
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Paclitaxel Treatment ◽  
Mcf 7

scholarly journals ARTEMISININ MODULATING EFFECT ON HUMAN BREAST CANCER CELL LINES WITH DIFFERENT SENSITIVITY TO CYTOSTATICS

2017 ◽  
Vol 39 (1) ◽  
pp. 25-29 ◽  
Author(s):  
V F Chekhun ◽  
N Yu Lukianova ◽  
T Borikun ◽  
T Zadvornyi ◽  
A Mokhir
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Iron Homeostasis ◽  
Chemotherapeutic Agents ◽  
Fold Change ◽  
Breast Cancer Cell Lines ◽  
Cellular Iron ◽  
Mcf 7

Aim: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin — Dox; cisplatin — DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. Materials and Methods: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid. The latter was added to modulate iron levels in the cells and explore its role in artemisinin-induced effects. The MTT assay was used to monitor cell viability, whereas changes of expression of selected proteins participating in regulation of cellular iron homeostasis were estimated using immunocytochemical methods. Finally, relative expression levels of miRNA-200b, -320a, and -34a were examined by using qRT-PCR. Results: Artemisinin affects mechanisms of the resistance of breast cancer cells towards both Dox and DDP at sub-toxic doses. The former drug induces changes of expression of iron-regulating proteins via different mechanisms, including epigenetic regulation. Particularly, the disturbances in ferritin heavy chain 1, lactoferrin, hepcidin (decrease) and ferroportin (increase) expression (р ≤ 0.05) were established. The most enhanced increase of miRNA expression under artemisinin influence were found for miRNA-200b in MCF-7/DDP cells (7.1 ± 0.98 fold change), miRNA-320a in MCF-7/Dox cells (2.9 ± 0.45 fold change) and miRNA-34a (1.7 ± 0.15 fold change) in MCF-7/S cells. It was observed that the sensitivity to artemisinin can be influenced by changing iron levels in cells. Conclusions: Artemisinin can modify iron metabolism of breast cancer cells by its cytotoxic effect, but also by inducing changes in expression of iron-regulating proteins and microRNAs (miRNAs), involved in their regulation. This modification affects the mechanisms that are implicated in drug-resistance, that makes artemisinin a perspective modulator of cell sensitivity towards chemotherapeutic agents in cancer treatment.

The secretome of non-tumorigenic mammary cells MCF-10A elicits DNA damage in MCF-7 and MDA-MB-231 breast cancer cells

2021 ◽  
Vol 70 ◽  
pp. 105018
Author(s):  
Guadalupe M. Vedoya ◽  
Marcela M. López Nigro ◽  
Gabriela A. Martín
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mammary Cells ◽  
Mcf 7

scholarly journals A ”Clickable” Probe for Active MGMT in Glioblastoma Demonstrates Two Discrete Populations of MGMT

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 453 ◽  
Author(s):  
Sudhir Raghavan ◽  
David S. Baskin ◽  
Martyn A. Sharpe
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cancer Cells ◽  
Dna Adducts ◽  
Alkylating Agents ◽  
Chemotherapeutic Agents ◽  
Dna Alkylation ◽  
Methylated Dna ◽  
Methylguanine Methyltransferase ◽  
Discrete Populations

Various pathways can repair DNA alkylation by chemotherapeutic agents such as temozolomide (TMZ). The enzyme O6-methylguanine methyltransferase (MGMT) removes O6-methylated DNA adducts, leading to the failure of chemotherapy in resistant glioblastomas. Because of the anti-chemotherapeutic activities of MGMT previously described, estimating the levels of active MGMT in cancer cells can be a significant predictor of response to alkylating agents. Current methods to detect MGMT in cells are indirect, complicated, time-intensive, or utilize molecules that require complex and multistep chemistry synthesis. Our design simulates DNA repair by the transfer of a clickable propargyl group from O6-propargyl guanine to active MGMT and subsequent attachment of fluorescein-linked PEG linker via ”click chemistry.” Visualization of active MGMT levels reveals discrete active and inactive MGMT populations with biphasic kinetics for MGMT inactivation in response to TMZ-induced DNA damage.

scholarly journals Feedback regulation of methyl methanesulfonate and ultraviolet-sensitive gene clone 81 via ATM/Chk2 pathway contributes to the resistance of MCF-7 breast cancer cells to cisplatin

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769430 ◽  
Author(s):  
Juan Lv ◽  
Ying Qian ◽  
Xiaoyan Ni ◽  
Xiuping Xu ◽  
Xuejun Dong
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Feedback Regulation ◽  
Double Strand Breaks ◽  
Gene Clone ◽  
Methyl Methanesulfonate ◽  
Strand Breaks ◽  
Damage Response ◽  
Dna Replication And Repair ◽  
Mcf 7

The methyl methanesulfonate and ultraviolet-sensitive gene clone 81 protein is a structure-specific nuclease that plays important roles in DNA replication and repair. Knockdown of methyl methanesulfonate and ultraviolet-sensitive gene clone 81 has been found to sensitize cancer cells to chemotherapy. However, the underlying molecular mechanism is not well understood. We found that methyl methanesulfonate and ultraviolet-sensitive gene clone 81 was upregulated and the ATM/Chk2 pathway was activated at the same time when MCF-7 cells were treated with cisplatin. By using lentivirus targeting methyl methanesulfonate and ultraviolet-sensitive gene clone 81 gene, we showed that knockdown of methyl methanesulfonate and ultraviolet-sensitive gene clone 81 enhanced cell apoptosis and inhibited cell proliferation in MCF-7 cells under cisplatin treatment. Abrogation of ATM/Chk2 pathway inhibited cell viability in MCF-7 cells in response to cisplatin. Importantly, we revealed that ATM/Chk2 was required for the upregulation of methyl methanesulfonate and ultraviolet-sensitive gene clone 81, and knockdown of methyl methanesulfonate and ultraviolet-sensitive gene clone 81 resulted in inactivation of ATM/Chk2 pathway in response to cisplatin. Meanwhile, knockdown of methyl methanesulfonate and ultraviolet-sensitive gene clone 81 activated the p53/Bcl-2 pathway in response to cisplatin. These data suggest that the ATM/Chk2 may promote the repair of DNA damage caused by cisplatin by sustaining methyl methanesulfonate and ultraviolet-sensitive gene clone 81, and the double-strand breaks generated by methyl methanesulfonate and ultraviolet-sensitive gene clone 81 may activate the ATM/Chk2 pathway in turn, which provide a novel mechanism of how methyl methanesulfonate and ultraviolet-sensitive gene clone 81 modulates DNA damage response and repair.

scholarly journals A Combination of an Antimitotic and a Bromodomain 4 Inhibitor Synergistically Inhibits the Metastatic MDA-MB-231 Breast Cancer Cell Line

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Thandi Mqoco ◽  
André Stander ◽  
Anna-Mart Engelbrecht ◽  
Anna M Joubert
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Current chemotherapeutic agents have many side effects and are toxic to normal cells, providing impetus to identify agents that can effectively eliminate tumorigenic cells without damaging healthy cells. The aim of this study was to examine whether combining a novel BRD4 inhibitor, ITH-47, with the antimitotic estradiol analogue, ESE-15-ol, would have a synergistic effect on inhibiting the growth of two different breast cancer cell lines in vitro. Our docking and molecular dynamics studies showed that compared to JQ1, ITH-47 showed a similar binding mode with hydrogen bonds forming between the ligand nitrogens of the pyrazole, ASN99, and water of the BRD4 protein. Data from cell growth studies revealed that the GI50 of ITH-47 and ESE-15-ol after 48 hours of exposure was determined to be 15 μM and 70 nM, respectively, in metastatic MDA-MB-231 breast cancer cells. In tumorigenic MCF-7 breast cancer cells, the GI50 of ITH-47 and ESE-15-ol was 75 μM and 60 nM, respectively, after 48 hours of exposure. Furthermore, the combination of 7.5 μM and 14 nM of ITH-47 and ESE-15-ol, respectively, resulted in 50% growth inhibition of MDA-MB-231 cells resulting in a synergistic combination index (CI) of 0.7. Flow cytometry studies revealed that, compared to the control, combination-treated MDA-MB-231 cells had significantly more cells present in the sub-G1 phase and the combination treatment induced apoptosis in the MDA-MB-231 cells. Compared to vehicle-treated cells, the combination-treated cells showed decreased levels of the BRD4, as well as c-Myc protein after 48 hours of exposure. In combination, the selective BRD4 inhibitor, ITH-47, and ESE-15-ol synergistically inhibited the growth of MDA-MB-231 breast cancer cells, but not of the MCF-7 cell line. This study provides evidence that resistance to BRD4 inhibitors may be overcome by combining inhibitors with other compounds, which may have treatment potential for hormone-independent breast cancers.

scholarly journals Specific downregulation of bcl-2 and xIAP by RNAi enhances the effects of chemotherapeutic agents in MCF-7 human breast cancer cells

2004 ◽  
Vol 11 (5) ◽  
pp. 309-316 ◽  
Author(s):  
Raquel T Lima ◽  
Luís M Martins ◽  
José E Guimarães ◽  
Clara Sambade ◽  
M Helena Vasconcelos
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

scholarly journals Cytotoxicity Effects ofAmoora rohitukaandchittagongaon Breast and Pancreatic Cancer Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Leo L. Chan ◽  
Sherine George ◽  
Irfan Ahmad ◽  
Saujanya L. Gosangari ◽  
Atiya Abbasi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Alternative Medicine ◽  
Cancer Cells ◽  
Antibacterial Properties ◽  
Chemotherapeutic Agents ◽  
Normal Fibroblast ◽  
Label Free ◽  
Anticancer Properties ◽  
Pancreatic Cancer Cells ◽  
Mcf 7

Chemotherapeutic agents for cancer are highly toxic to healthy tissues and hence alternative medicine avenues are widely researched. Majority of the recent studies on alternative medicine suggested thatAmoora rohitukapossesses considerable antitumor and antibacterial properties. In this work,rohitukaandchittagonga, fractionated with petroleum ether, dichloromethane, and ethanol, were explored for their anticancer potential against two breast cancer (MCF-7 and HTB-126) and three pancreatic cancer (Panc-1, Mia-Paca2, and Capan1). The human foreskin fibroblast, Hs68, was also included. Cytotoxicity of each extract was analyzed using the MTT assay and label-free photonic crystal biosensor assay. A concentration series of each extract was performed on the six cell lines. For MCF-7 cancer cells, thechittagonga(Pet-Ether and CH2Cl2) androhituka(Pet-Ether) extracts induced cytotoxicity; thechittagonga(EtoAC) androhituka(MeOH) extracts did not induce cytotoxicity. For HTB126, Panc-1, Mia-Paca2, and Capan-1 cancer cells, only thechittagongaCH2Cl2extract showed a significant cytotoxic effect. The extracts were not cytotoxic to normal fibroblast Hs68 cells, which may be correlated to the specificity ofAmooraextracts in targeting cancerous cells. Based on these results, further examination of the potential anticancer propertiesAmooraspecies and the identification of the active ingredients of these extracts is warranted.

scholarly journals MELK-T1, a small-molecule inhibitor of protein kinase MELK, decreases DNA-damage tolerance in proliferating cancer cells

2015 ◽  
Vol 35 (6) ◽  
Author(s):  
Lijs Beke ◽  
Cenk Kig ◽  
Joannes T. M. Linders ◽  
Shannah Boens ◽  
An Boeckx ◽  
...  
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Small Molecule ◽  
Damage Tolerance ◽  
Replication Stress ◽  
Small Molecule Inhibitor ◽  
Dna Damage Tolerance ◽  
Molecule Inhibitor ◽  
Senescence Phenotype

Protein kinase MELK has oncogenic properties and is highly overexpressed in some tumors. In the present study, we show that a novel MELK inhibitor causes both the inhibition and degradation of MELK, culminating in replication stress and a senescence phenotype.

Processing of clustered DNA damage in human breast cancer cells MCF-7 with partial DNA-PKcs deficiency

2008 ◽  
Vol 269 (1) ◽  
pp. 174-183 ◽  
Author(s):  
Prakash Peddi ◽  
Dave C. Francisco ◽  
Angela M. Cecil ◽  
Jessica M. Hair ◽  
Mihalis I. Panayiotidis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Clustered Dna Damage ◽  
Mcf 7
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