scholarly journals Inhibition of GSK-3β activity can result in drug and hormonal resistance and alter sensitivity to targeted therapy in MCF-7 breast cancer cells

Cell Cycle ◽  
2014 ◽  
Vol 13 (5) ◽  
pp. 820-833 ◽  
Author(s):  
Melissa Sokolosky ◽  
William H Chappell ◽  
Kristin Stadelman ◽  
Stephen L Abrams ◽  
Nicole M Davis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Hormonal Resistance ◽  
Gsk 3Β ◽  
Mcf 7

scholarly journals GSK-3β Can Regulate the Sensitivity of MIA-PaCa-2 Pancreatic and MCF-7 Breast Cancer Cells to Chemotherapeutic Drugs, Targeted Therapeutics and Nutraceuticals

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 816
Author(s):  
Stephen L. Abrams ◽  
Shaw M. Akula ◽  
Akshaya K. Meher ◽  
Linda S. Steelman ◽  
Agnieszka Gizak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Cancer Cells ◽  
Mitochondrial Respiration ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Drugs ◽  
Pancreatic Cancers ◽  
Signal Transduction Inhibitors ◽  
Gsk 3Β ◽  
Mcf 7

Glycogen synthase kinase-3 (GSK-3) is a regulator of signaling pathways. KRas is frequently mutated in pancreatic cancers. The growth of certain pancreatic cancers is KRas-dependent and can be suppressed by GSK-3 inhibitors, documenting a link between KRas and GSK-3. To further elucidate the roles of GSK-3β in drug-resistance, we transfected KRas-dependent MIA-PaCa-2 pancreatic cells with wild-type (WT) and kinase-dead (KD) forms of GSK-3β. Transfection of MIA-PaCa-2 cells with WT-GSK-3β increased their resistance to various chemotherapeutic drugs and certain small molecule inhibitors. Transfection of cells with KD-GSK-3β often increased therapeutic sensitivity. An exception was observed with cells transfected with WT-GSK-3β and sensitivity to the BCL2/BCLXL ABT737 inhibitor. WT-GSK-3β reduced glycolytic capacity of the cells but did not affect the basal glycolysis and mitochondrial respiration. KD-GSK-3β decreased both basal glycolysis and glycolytic capacity and reduced mitochondrial respiration in MIA-PaCa-2 cells. As a comparison, the effects of GSK-3 on MCF-7 breast cancer cells, which have mutant PIK3CA, were examined. KD-GSK-3β increased the resistance of MCF-7 cells to chemotherapeutic drugs and certain signal transduction inhibitors. Thus, altering the levels of GSK-3β can have dramatic effects on sensitivity to drugs and signal transduction inhibitors which may be influenced by the background of the tumor.

scholarly journals COMPARATIVE ANALYSIS OF THE EXOSOMAL CARGO OF THE ESTROGEN-RESISTANT BREAST CANCER CELLS

2018 ◽  
Vol 17 (4) ◽  
pp. 36-40 ◽  
Author(s):  
S. E. Semina ◽  
N. A. Barlev ◽  
A. G. Mittenberg ◽  
M. A. Krasilnikov
Keyword(s):  
Breast Cancer ◽  
Comparative Analysis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Protein Composition ◽  
Tamoxifen Treatment ◽  
Transfer Resistance ◽  
Exosomal Mirnas ◽  
Hormonal Resistance ◽  
Mcf 7

The exosomes involvement in the pathogenesis of tumors is based on their property to incorporate into the recipient cells resulting in the both genomic and epigenomic changes.  Earlier we have shown that exosomes from different types of estrogen-independent breast  cancer cells (MCF-7/T developed by long-term tamoxifen treatment, and MCF-7/M)  developed by metformin treatment were able to transfer resistance to the parent MCF-7  cells. To elucidate the common features of the both types of resistant exosomes, the  proteome and microRNA cargo of the control and both types of the resistant exosomes were  analyzed. Totally, more than 400 proteins were identified in the exosome samples. Of these  proteins, only two proteins, DMBT1 (Deleted in Malignant Brain Tumors 1) and THBS1  (Thrombospondin-1), were commonly expressed in the both resistant exosomes (less than  5% from total DEPs) demonstrating the unique protein composition of each type of the resistant exosomes. The comparative analysis of the miRNA differentially expressed in  the both MCF-7/T and MCF-7/M resistant exosomes revealed 180 up-regulated and 202  down-regulated miRNAs. Among them, 4 up-regulated and 8 down-regulated miRNAs were  associated with progression of hormonal resistance of breast tumors. The bioinformatical  analysis of 4 up-regulated exosomal miRNAs revealed 2 miRNAs, mir- 101and mir-181b, which up-regulated PI3K signaling  supporting the key role of PI3K/Akt in the development of the resistant phenotype of breast cancer cells.

scholarly journals CHANGES IN DNA METHYLATION PROFILE IN TAMOXIFEN-RESISTANT MCF-7 SUBLINES

2019 ◽  
Vol 18 (5) ◽  
pp. 45-53
Author(s):  
О. Е. Andreeva ◽  
V. О. Sigin ◽  
V. V. Strelnikov ◽  
A. S. Tanas ◽  
A. M. Scherbakov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Secondary Resistance ◽  
Resistant Phenotype ◽  
Hormonal Resistance ◽  
Mcf 7 ◽  
In Cells ◽  
Resistant Cells

Abstract Introduction. We have previously shown the feasibility of hormonal resistance horizontal distribution from cell to cell, with the joint cultivation of sensitive and resistant cells and/or through exosomes secreted by resistant cells. What is the mechanism of such resistance distribution, and how do cells with secondary resistance reproduce the characteristics of donor resistant cells? To answer these questions, we analyzed the overall level of DNA methylation in MCF-7 estrogen-dependent breast cancer cells and estrogen-independent sublinia.The purpose of the study was to analyze DNA methylation profiles for the development of hormonal resistance by breast cancer cells and for resistant phenotype further accession.Methods. DNA methylation was evaluated by the RRBS (Reduced Representation Bisulfite Sequencing) method in MCF-7 breast cancer cells and their resistant sublines.Results. 19 CpG dinucleotides, differentially and generally unidirectionally methylated in cells with primary and secondary resistance to tamoxifen, were detected. Differential changes in methylation were found for DNA regions that regulated the expression of six protein-coding genes: PRKCZ, TRAPPC9, AS IC2, C2CD4A, ZNF787, CRTAC 1. Bioinformatics analysis showed that two of these six genes, PRKCZ (protein kinase C Zeta) and TRAPPC9 (Trafficking Protein Particle Complex Subunit 9) were directly involved in the regulation of NF-κB activity.Conclusion. The data obtained indicate the existence of common DNA patterns, the methylation of which varies in the same direction in cells with primary and secondary resistance. The involvement of two of the identified genes in the regulation of NF-κB may indicate the inclusion of the latter in the formation of a resistant phenotype of tumor cells, even under conditions of horizontal transfer of resistance.

Mechanism research on the lupeol treatment on MCF-7 breast cancer cells based on cell metabonomics

2014 ◽  
Vol 32 (3) ◽  
pp. 278
Author(s):  
Dongdong SHI ◽  
Yuanyuan KUANG ◽  
Guiming WANG ◽  
Zhangxiao PENG ◽  
Yan WANG ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mechanism Research ◽  
Mcf 7

Anticancer Potential of Calli Versus Seedling Extracts Derived from Rosmarinus officinalis and Coleus hybridus

2020 ◽  
Vol 21 (14) ◽  
pp. 1528-1538
Author(s):  
Sarah Albogami ◽  
Hadeer Darwish ◽  
Hala M. Abdelmigid ◽  
Saqer Alotaibi ◽  
Ahmed Nour El-Deen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Transcriptional Profiling ◽  
Significant Inhibition ◽  
Rosmarinus Officinalis ◽  
Crude Extracts ◽  
Incidence And Mortality ◽  
Mcf 7

Background: In Saudi Arabia, the incidence and mortality rates of breast cancer are high. Although current treatments are effective, breast cancer cells develop resistance to these treatments. Numerous studies have demonstrated that active compounds in plant extracts, such as the phenolic compound Rosmarinic Acid (RA), exert anti-cancer effects. Objective: We investigated the anticancer properties of methanolic crude extracts of seedlings and calli of Rosmarinus officinalis and Coleus hybridus, two Lamiaceae species. Methods: MCF-7 human breast cancer cells were treated with methanolic crude extracts obtained from plant calli and seedlings generated in vitro, and cell proliferation was evaluated. Transcriptional profiling of the seedling and callus tissues was also conducted. Results: The mRNA expression levels of RA genes were higher in C. hybridus seedlings than in R. officinalis seedlings, as well as in C. hybridus calli than in R. officinalis calli, except for TAT and C4H. In addition, seedling and callus extracts of both R. officinalis and C. hybridus showed anti-proliferative effects against MCF-7 cells after 24 or 48 h of treatment. Discussion: At a low concentration of 10 μg/mL, C. hybridus calli and seedling extracts showed the most significant anti-proliferative effects after 24 and 48 h of exposure (p < 0.01); controls (doxorubicin) also showed significant inhibition, but lesser than that observed with C. hybridus (p < 0.05). Results with R. officinalis callus and seedling extracts did not significantly differ from those with untreated cells. Conclusion: Methanolic extracts of R. officinalis and C. hybridus are potentially valuable options for breast cancer treatment.

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