scholarly journals Role of autophagy and lysosomal drug sequestration in acquired resistance to doxorubicin in MCF-7 cells

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Baoqing Guo ◽  
Adam Tam ◽  
Stacey A. Santi ◽  
Amadeo M. Parissenti
Keyword(s):  
Acquired Resistance ◽  
Drug Sequestration ◽  
Resistance To Doxorubicin ◽  
Mcf 7

scholarly journals Iron metabolism disturbances in the MCF-7 human breast cancer cells with acquired resistance to doxorubicin and cisplatin

2013 ◽  
Vol 43 (5) ◽  
pp. 1481-1486 ◽  
Author(s):  
VASYL F. CHEKHUN ◽  
NATALIA Yu. LUKYANOVA ◽  
ANATOLIY P. BURLAKA ◽  
NATALIA A. BEZDENEZHNYKH ◽  
SVITLANA I. SHPYLEVA ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Iron Metabolism ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Acquired Resistance ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Resistance To Doxorubicin ◽  
Mcf 7

scholarly journals Role of Differentially Expressed Proteins in Acquired Resistance to Cdk4/6 Inhibitor in Breast Cancer

2021 ◽  
Author(s):  
Binayak Kumar ◽  
Peeyush Prasad ◽  
Ragini Singh ◽  
Ram Krishana Sahu ◽  
Ashutosh Singh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Targets ◽  
Acquired Resistance ◽  
Therapy Resistance ◽  
Resistant Cell ◽  
Molecular Signature ◽  
Mcf 7 ◽  
Resistant Cells

Abstract CDK4/6 inhibitors (Abemaciclib, Ab and Palbociclib, Pb) stop the G1-phase in cell-cycle being used to cure advanced stage of breast cancer (BC). Acquired resistance is a major challenge in BC therapy. The molecular signature of the therapy resistance for Ab and Pb drugs in BC should be explored. Here, we developed Ab/Pb-resistant cell-models and explored the molecular changes. Drug’s resistance cells were developed in MCF-7 cells by continuous drug treatment and it was confirmed by MTT-assay, PI-staining-microscopy, and real-time-qPCR. Global proteome profiling done by Labelled-free-Proteome-Orbitrap-Fusion-MS-MS technique. Bioinformatics tools used to analyse the proteome data. Ab-resistant and Pb-resistant MCF-7 cells showed increased tolerance for the respective drug. The BCL-2 and MCL-1 survival genes were up-regulated, while the apoptosis genes BAD, BAX, CASP-3 and PARP-1were down-regulated in the resistant cells. Expression of the MDR-1, ABCG2, ESR-1, CDK4, CDK6, and Cyclin-D1 genes were increased in both resistance cells. For proteomics, 237 and 239 proteins were expressed differently in the resistant Ab and Pb cells, respectively. The NUDT5, PEPD, ABAT, ATP1B1, GGCT, and SELENBP1 proteins were down-regulated and the SBSN, HSD17B10, CD9, PDIA3, PSMB4, SLC2A1, and VTN proteins were up-regulated in Ab-resistant cells. The NUDT5, PEPD, and GGCT proteins were down-regulated, while CD47, HIST1H2BN, LMNA, VTN, PSMB5, HBB, PSMA7, FLNB, PRDX4, VDAC1, GOT2, HSPA5, SERPINH1, EIF4A2, FTH, and VIM proteins were up-regulated in Pb-resistant cells. These proteins are a new set of prognostic markers and drug targets for overcoming the respective drug resistance. However, it is necessary to perform an in vivo or clinical assessment.

Role of DNA hypomethylation in the development of the resistance to doxorubicin in human MCF-7 breast adenocarcinoma cells

2006 ◽  
Vol 231 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Vasil F. Chekhun ◽  
Galina I. Kulik ◽  
Olga V. Yurchenko ◽  
Volodymyr P. Tryndyak ◽  
Igor N. Todor ◽  
...  
Keyword(s):  
Breast Adenocarcinoma ◽  
Dna Hypomethylation ◽  
Adenocarcinoma Cells ◽  
Resistance To Doxorubicin ◽  
Mcf 7

scholarly journals Hypoxia‐Induced Acidification Causes Mitoxantrone Resistance Not Mediated by Drug Transporters in Human Breast Cancer Cells

2005 ◽  
Vol 27 (1) ◽  
pp. 43-49
Author(s):  
A. E. Greijer ◽  
M. C. de Jong ◽  
G. L. Scheffer ◽  
A. Shvarts ◽  
P. J. van Diest ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Drug Transporters ◽  
Human Breast ◽  
Protein Levels ◽  
Resistance To Doxorubicin ◽  
Resistance To Chemotherapy ◽  
Mcf 7

Hypoxia has clinically been associated with resistance to chemotherapy. The aim of this study was to investigate whether hypoxia induces resistance to doxorubicin and mitoxantrone, two common drugs in cancer treatment, in MCF‐7 breast cancer cells, and SW1573 non‐small lung cancer cells. In addition, the role of drug transporters P‐gp, BCRP and MRP1 was analysed. Hypoxia induced resistance in MCF‐7 cells to mitoxantrone shifted the IC50 value from 0.09 μM (±0.01) to 0.54 μM (±0.06) under hypoxia, whereas survival of MCF‐7 and SW1573 cells in the presence of doxorubicin was not altered. Accumulation of mitoxantrone and daunorubicin, a doxorubicin fluorescent homologue, appeared to be 5.3 and 3.2 times lower in MCF‐7 cells, respectively. Cytotoxicity assays showed no increased functionality of the drug transporters P‐gp, BCRP and MRP1 under hypoxia. In addition, protein levels of these drug transporters were not changed. Medium of the MCF‐7 cells became more acidic under hypoxia thereby causing a decreased uptake of mitoxantrone. Hypoxia induces mitoxantrone resistance in MCF‐7 cells not mediated by the three major MDR transporters. Hypoxia‐induced acidification may cause this resistance by decreased cellular uptake together with a lowered cytotoxicity due to pH‐dependent topoisomerase type II activity.

scholarly journals The inhibitory role of synthesized Nickel oxide nanoparticles against Hep-G2, MCF-7, and HT-29 cell lines: the inhibitory role of NiO NPs against Hep-G2, MCF-7, and HT-29 cell lines

2021 ◽  
Vol 14 (3) ◽  
pp. 443-453
Author(s):  
Mohammad Amin Jadidi Kouhbanani ◽  
Yasin Sadeghipour ◽  
Mina Sarani ◽  
Erfan Sefidgar ◽  
Saba Ilkhani ◽  
...  
Keyword(s):  
Nickel Oxide ◽  
Cell Lines ◽  
Oxide Nanoparticles ◽  
Hep G2 ◽  
Nickel Oxide Nanoparticles ◽  
Inhibitory Role ◽  
Nio Nps ◽  
Ht 29 ◽  
Mcf 7

scholarly journals LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Feifei Zhang ◽  
Hui Wang ◽  
Jiang Yu ◽  
Xueqing Yao ◽  
Shibin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Alternative Splicing ◽  
Noncoding Rna ◽  
De Novo ◽  
Acquired Resistance ◽  
Genetic Alterations ◽  
Clinical Samples ◽  
Autophagy Flux ◽  
Resistance To Chemotherapy

AbstractDe novo and acquired resistance, which are mainly mediated by genetic alterations, are barriers to effective routine chemotherapy. However, the mechanisms underlying gastric cancer (GC) resistance to chemotherapy are still unclear. We showed that the long noncoding RNA CRNDE was related to the chemosensitivity of GC in clinical samples and a PDX model. CRNDE was decreased and inhibited autophagy flux in chemoresistant GC cells. CRNDE directly bound to splicing protein SRSF6 to reduce its protein stability and thus regulate alternative splicing (AS) events. We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.

scholarly journals Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2547
Author(s):  
Keunsoo Kang ◽  
Yoonjung Choi ◽  
Hyeonjin Moon ◽  
Chaelin You ◽  
Minjin Seo ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Homologous Recombination ◽  
Cell Lines ◽  
Regulatory Elements ◽  
Binding Motif ◽  
Genome Wide ◽  
E Box ◽  
Autophagy Pathway ◽  
Mcf 7

RAD51 is a recombinase that plays a pivotal role in homologous recombination. Although the role of RAD51 in homologous recombination has been extensively studied, it is unclear whether RAD51 can be involved in gene regulation as a co-factor. In this study, we found evidence that RAD51 may contribute to the regulation of genes involved in the autophagy pathway with E-box proteins such as USF1, USF2, and/or MITF in GM12878, HepG2, K562, and MCF-7 cell lines. The canonical USF binding motif (CACGTG) was significantly identified at RAD51-bound cis-regulatory elements in all four cell lines. In addition, genome-wide USF1, USF2, and/or MITF-binding regions significantly coincided with the RAD51-associated cis-regulatory elements in the same cell line. Interestingly, the promoters of genes associated with the autophagy pathway, such as ATG3 and ATG5, were significantly occupied by RAD51 and regulated by RAD51 in HepG2 and MCF-7 cell lines. Taken together, these results unveiled a novel role of RAD51 and provided evidence that RAD51-associated cis-regulatory elements could possibly be involved in regulating autophagy-related genes with E-box binding proteins.

scholarly journals Transient Receptor Potential C 1/4/5 Is a Determinant of MTI-101 Induced Calcium Influx and Cell Death in Multiple Myeloma

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1490
Author(s):  
Osama M. Elzamzamy ◽  
Brandon E. Johnson ◽  
Wei-Chih Chen ◽  
Gangqing Hu ◽  
Reinhold Penner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Transient Receptor Potential ◽  
Cyclic Peptide ◽  
Calcium Influx ◽  
Acquired Resistance ◽  
Treatment Strategies ◽  
Prognostic Indicators ◽  
Causative Role

Multiple myeloma (MM) is a currently incurable hematologic cancer. Patients that initially respond to therapeutic intervention eventually relapse with drug resistant disease. Thus, novel treatment strategies are critically needed to improve patient outcomes. Our group has developed a novel cyclic peptide referred to as MTI-101 for the treatment of MM. We previously reported that acquired resistance to HYD-1, the linear form of MTI-101, correlated with the repression of genes involved in store operated Ca2+ entry (SOCE): PLCβ, SERCA, ITPR3, and TRPC1 expression. In this study, we sought to determine the role of TRPC1 heteromers in mediating MTI-101 induced cationic flux. Our data indicate that, consistent with the activation of TRPC heteromers, MTI-101 treatment induced Ca2+ and Na+ influx. However, replacing extracellular Na+ with NMDG did not reduce MTI-101-induced cell death. In contrast, decreasing extracellular Ca2+ reduced both MTI-101-induced Ca2+ influx as well as cell death. The causative role of TRPC heteromers was established by suppressing STIM1, TRPC1, TRPC4, or TRPC5 function both pharmacologically and by siRNA, resulting in a reduction in MTI-101-induced Ca2+ influx. Mechanistically, MTI-101 treatment induces trafficking of TRPC1 to the membrane and co-immunoprecipitation studies indicate that MTI-101 treatment induces a TRPC1-STIM1 complex. Moreover, treatment with calpeptin inhibited MTI-101-induced Ca2+ influx and cell death, indicating a role of calpain in the mechanism of MTI-101-induced cytotoxicity. Finally, components of the SOCE pathway were found to be poor prognostic indicators among MM patients, suggesting that this pathway is attractive for the treatment of MM.

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