miR-34a Reverses Doxorubicin Resistance in Breast Cancer

2020 ◽  
Vol 10 (12) ◽  
pp. 1820-1826
Author(s):  
Guolin Ye ◽  
Suqun He ◽  
Ruilin Pan ◽  
Lewei Zhu ◽  
Dan Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Survival Rate ◽  
Cancer Cell Line ◽  
Combination Group ◽  
Tumor Resistance ◽  
Chemotherapy Drugs ◽  
Resistant Strains ◽  
Doxorubicin Group

Chemotherapy is effectively used for treating breast cancer, but the problem of tumor resistance to chemotherapy drugs has been plaguing scientists. Our study investigated miR-34a?s effect on the sensitivity of drug-resistant strains to chemotherapeutic drugs using doxorubicin-resistant strains of breast cancer cells. Cell survival rate was detected by MTT assay. The doxorubicin-resistant strain rMCF-7 was obtained. The cell scratching method and CCK-8 method were used to detect cell migration and proliferation.Western Blot was performed for measuring SIRT1, p-AKT, AKT, p-mTOR and mTOR level. miR-34a significantly reduced the survival rate o doxorubicin-resistant breast cancer cell line rMCF-7 and significantly enhanced doxorubicin?s effect on inhibiting cell proliferation and cell migration. Compared with the doxorubicin group alone, miR-34a and doxorubicin combination group significantly downregulated SIRT1, p-AKT/AKT and p-mTOR/mTOR related proteins in rMCF-7 cells. miR-34a can reverse the resistance of doxorubicin in breast cancer in vitro and the mechanism may be through inhibition of SIRT and AKT signaling.

scholarly journals Quantification of cancer cell migration with an integrated experimental-computational pipeline

2017 ◽  
Author(s):  
Edwin F. Juarez ◽  
Carolina Garri ◽  
Ahmadreza Ghaffarizadeh ◽  
Paul Macklin ◽  
Kian Kani
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Migration ◽  
Computational Pipeline ◽  
Migration Assay ◽  
User Friendly ◽  
Migration Of Cells

AbstractWe describe an integrated experimental-computational pipeline for quantifying cell migration in vitro. This pipeline is robust to image noise, open source, and user friendly. The experimental component uses the Oris cell migration assay (Platypus Technologies) to create migration regions. The computational component of the pipeline creates masks in Matlab (MathWorks) to cell-covered regions, uses a genetic algorithm to automatically select the migration region, and outputs a metric to quantify the migration of cells. In this work we demonstrate the utility of our pipeline by quantifying the effects of a drug (Taxol) and of the secreted Anterior Gradient 2 (sAGR2) protein in the migration of MDA-MB-231 cells (a breast cancer cell line). In particular, we show that blocking sAGR2 reduces migration of MDA-MB-231 cells.

scholarly journals Vγ9Vδ2 T Cells Strengthen Cisplatin Inhibition Activity Against Breast Cancer MDA-MB-231 Cells by Destructing Mitochondrial Function and Cell Ultrastructure

2020 ◽  
Author(s):  
Xin Huang ◽  
Cunchuan Wang ◽  
Ningxia Wang
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Mitochondrial Function ◽  
System Development ◽  
Cancer Cell Line ◽  
Chemotherapy Drugs ◽  
Immune System Development ◽  
Vγ9vδ2 T Cells

Abstract Background: Breast cancer ranks second of new cases and fifth of death in 2018 world widely. Chemotherapy, one of cancer therapeutic strategies, plays important role in controlling mortality of breast cancer. Cis-platinum (CDDP), one of traditional chemotherapy drugs, had been used clinically for years. The crucial limitation of CDDP is due to its adverse effects on immune system. Development of new protocol that can minimize side effect and meanwhile elevate clinical efficacy of traditional drug like CDDP will eventually benefit cancer patients. Vγ9Vδ2 T cells had been reported to be able to up-regulate immune function of cancer patients, therefore, our hypothesis is that introduction of Vγ9Vδ2 T cells could potentiate CDDP efficacy against breast cancer. Methods: In the present work, breast cancer cell line MDA-MB-231 was used a model cell to test our hypothesis. The therapeutic dose of CDDP in vitro was analyzed by flow cytometry; The cytoskeleton was visualized by using a confocal microscopy, and the ultrastructure of the membrane was observed by atomic force microscopy to observe the effect of combined action on MDA-MB-231 cells; The mitochondrial function of MDA-MB-231 cells was detected, and the relevant mechanism of Vγ9Vδ2 T in enhancing cisplatin cells' inhibition of MDA-MB-231 cells was discussed. Results: Vγ9Vδ2 T cells could enhance CDDP-induced MDA-MB-231 cell membrane ultrastructure disorder and cytoskeleton disorder, and enhance the inhibition of CDDP on MDA-MB-231 cells, of which Vγ9Vδ2 T cells enhancing CDDP-induced mitochondrial dysfunction was one of its mechanisms. Conclusion: In this study，the mechanism of Vγ9Vδ2 T cells in enhancing the inhibition of cisplatin on MDA-MB-231 cells was studied, which could provide an important scientific clue for developing effective treatment schemes for breast cancer, especially the refractory TNBC breast cancer, based on Vγ9Vδ2 T cells in the future.

scholarly journals E2F1 Drives Breast Cancer Metastasis by Regulating the Target Gene FGF13 and Altering Cell Migration

2019 ◽  
Author(s):  
Daniel P. Hollern ◽  
Matthew R. Swiatnicki ◽  
Jonathan P. Rennhack ◽  
Sean A. Misek ◽  
Brooke C. Matson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Pulmonary Metastasis ◽  
Target Gene ◽  
Cancer Metastasis ◽  
Target Genes ◽  
Cancer Cell Line ◽  
Breast Cancer Metastasis ◽  
E2f Transcription Factors

ABSTRACTIn prior work we demonstrated that loss of E2F transcription factors inhibits metastasis. Here we address the mechanisms for this phenotype and identify the E2F regulated genes that coordinate tumor cell metastasis. Transcriptomic profiling of E2F1 knockout tumors identified a role for E2F1 as a master regulator of a suite of pro-metastatic genes, but also uncovered E2F1 target genes with an unknown role in pulmonary metastasis. High expression of one of these genes, Fgf13, is associated with early human breast cancer metastasis in a clinical dataset. Together these data led to the hypothesis that Fgf13 is critical for breast cancer metastasis, and that upregulation of Fgf13 may partially explain how E2F1 promotes breast cancer metastasis. To test this hypothesis we ablated Fgf13 via CRISPR. Deletion of Fgf13 in a MMTV-PyMT breast cancer cell line reduces the frequency of pulmonary metastasis. In addition, loss of Fgf13 reduced in vitro cell migration, suggesting that Fgf13 may be critical for tumor cells to invade out of and escape the primary tumor. The significance of this work is twofold: we have both uncovered genomic features by which E2F1 regulates metastasis and we have identified new pro-metastatic functions for the E2F1 target gene Fgf13.

scholarly journals Quantification of cancer cell migration with an integrated experimental-computational pipeline

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1296 ◽  
Author(s):  
Edwin F Juarez ◽  
Carolina Garri ◽  
Ahmadreza Ghaffarizadeh ◽  
Paul Macklin ◽  
Kian Kani
Keyword(s):  
Breast Cancer ◽  
Genetic Algorithm ◽  
Cell Migration ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Migration ◽  
Computational Pipeline ◽  
Migration Assay ◽  
User Friendly

We describe an integrated experimental-computational pipeline for quantifying cell migration in vitro. This pipeline is robust to image noise, open source, and user friendly. The experimental component uses the Oris cell migration assay (Platypus Technologies) to create migration regions. The computational component of the pipeline creates masks in Matlab (MathWorks) to cell-covered regions, uses a genetic algorithm to automatically select the migration region, and outputs a metric to quantify cell migration. In this work we demonstrate the utility of our pipeline by quantifying the effects of a drug (Taxol) and of the extracellular Anterior Gradient 2 (eAGR2) protein on the migration of MDA-MB-231 cells (a breast cancer cell line). In particular, we show that inhibiting eAGR2 reduces migration of MDA-MB-231 cells.

A Novel Triazole Derivative Drug Presenting In Vitro and In Vivo Anticancer Properties

2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Hepatic Function ◽  
Anticancer Properties ◽  
Mcf 7

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.

scholarly journals The inhibitory potency of isoxazole-curcumin analogue for the management of breast cancer: A comparative in vitro and molecular modeling investigation

2021 ◽  
Author(s):  
Fiona C. Rodrigues ◽  
N. V. Anil Kumar ◽  
Gangadhar Hari ◽  
K. S. R. Pai ◽  
Goutam Thakur
Keyword(s):  
Breast Cancer ◽  
Herbal Remedy ◽  
Cancer Cell Line ◽  
Heterocyclic Ring ◽  
Regulatory Role ◽  
Multiple Traits ◽  
One Pot ◽  
Anticancer Efficacy ◽  
Improved Stability

AbstractCurcumin, a potent phytochemical derived from the spice element turmeric, has been identified as a herbal remedy decades ago and has displayed promise in the field of medicinal chemistry. However, multiple traits associated with curcumin, such as poor bioavailability and instability, limit its effectiveness to be accepted as a lead drug-like entity. Different reactive sites in its chemical structure have been identified to incorporate modifications as attempts to improving its efficacy. The diketo group present in the center of the structural scaffold has been touted as the group responsible for the instability of curcumin, and substituting it with a heterocyclic ring contributes to improved stability. In this study, four heterocyclic curcumin analogues, representing some broad groups of heterocyclic curcuminoids (isoxazole-, pyrazole-, N-phenyl pyrazole- and N-amido-pyrazole-based), have been synthesized by a simple one-pot synthesis and have been characterized by FTIR, 1H-NMR, 13C-NMR, DSC and LC–MS. To predict its potential anticancer efficacy, the compounds have been analyzed by computational studies via molecular docking for their regulatory role against three key proteins, namely GSK-3β—of which abnormal regulation and expression is associated with cancer; Bcl-2—an apoptosis regulator; and PR which is a key nuclear receptor involved in breast cancer development. One of the compounds, isoxazole-curcumin, has consistently indicated a better docking score than the other tested compounds as well as curcumin. Apart from docking, the compounds have also been profiled for their ADME properties as well as free energy binding calculations. Further, the in vitro cytotoxic evaluation of the analogues was carried out by SRB assay in breast cancer cell line (MCF7), out of which isoxazole-curcumin (IC50–3.97 µM) has displayed a sevenfold superior activity than curcumin (IC50–21.89 µM). In the collation of results, it can be suggested that isoxazole-curcumin behaves as a potential lead owing to its ability to be involved in a regulatory role with multiple significant cancer proteins and hence deserves further investigations in the development of small molecule-based anti-breast cancer agents. Graphic abstract

scholarly journals Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Click Reaction ◽  
Chemotherapy Drugs ◽  
Targeting Peptide ◽  
And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

scholarly journals Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1303
Author(s):  
Rizwan Ali ◽  
Hajar Al Zahrani ◽  
Tlili Barhoumi ◽  
Alshaimaa Alhallaj ◽  
Abdullah Mashhour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cell Line ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cell Line ◽  
Triple Negative ◽  
Cancer Cell Line

In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells’ expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.

In vitro toxicological assessment of flumethrin’s effects on MCF-7 breast cancer cells

2021 ◽  
pp. 096032712110227
Author(s):  
S Kara-Ertekin ◽  
S Yazar ◽  
M Erkan
Keyword(s):  
Breast Cancer ◽  
Cancer Cell Line ◽  
Tail Length ◽  
Tail Moment ◽  
High Concentration ◽  
Toxicological Assessment ◽  
Estrogenic Effects ◽  
Pyrethroid Pesticides ◽  
Mcf 7

Pyrethroid pesticides are frequently used for household insect control of insects and in agriculture and livestock. Flumethrin is a pyrethroid that is used against ectoparasites in many animals. The goal of this study was to evaluate the cytotoxic, apoptotic, genotoxic, and estrogenic effects of flumethrin on the mammalian breast cancer cell line (MCF-7). Compared with control groups, a dose-dependent decrease was observed in cell viability at concentrations of 100 µM and higher. The cytotoxic and apoptotic effects detected by LDH assay and AO/EtBr staining increased significantly at a concentration of 1000 µM. The expression of BCL2, which is an anti-apoptotic gene, significantly decreased, whereas BAX, TP53, and P21 expression significantly increased. The results of a comet assay indicated that flumethrin significantly changed tail length, tail % DNA, tail moment, and Olive tail moment in concentrations above 1 and 10 µM. In addition, a 0.1 µM concentration of flumethrin affected ERα receptor mediated cell proliferation and increased transcription of estrogen-responsive pS2 (TFF1) and progesterone receptor (PGR) genes. As a result, flumethrin-induced apoptosis and cytotoxicity at a high concentration, while induced genotoxicity even at lower concentrations. Flumethrin is an endocrine disrupting insecticide with estrogenic effects at very low concentrations.

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