scholarly journals The Dicyano Compound Induces Autophagic or Apoptotic Cell Death Via Twıst/C-Myc Axis Depending on Metastatic Characteristics of Breast Cancer Cells

Author(s):  
Ozge ALVUR ◽  
Hakan KUCUKSAYAN ◽  
Yasemin BAYGU ◽  
Nilgun KABAY ◽  
Yasar GOK ◽  
...  

Abstract Breast cancer is a heterogeneous disease which has distinct subtypes and therefore development of novel targeting treatments to fight aganist breast cancer is needed. Although autophagy and apoptosis considered as the major programmed cell death mechanisms are among the current target mechanisms, there are some difficulties in clinical treatment such as the development of drug resistance and cancer recurrence. Therefore it is important that illumination of distinctive mechanisms between cancer types for development novel treatment strategies. In this study, we examined the anti-proliferative effects of the triazole linked galactose substituted dicyano compound (hereafter referred to as the dicyano compound (the DC)) on two different breast cancer cell lines, MDA-MB-231 and MCF-7. We determined that response of each cell lines to the DC was different, since autophagy was induced in MDA-MB-231 and apoptosis was induced in MCF-7. For this reason, we hypothesized that these different responses may be due to the different characteristics of the cells and evaluated effects of aggresiveness degrees of both cell lines on response to the DC. As a result of our analysis, we determined that c-Myc regulation in both cell lines was different upon the DC treatment depending on expression of Twist, an epithelial-to-mesenchymal transition (EMT) mediator. Therefore, we suggest that Twist/c-Myc axis may have a role in different response to the DC-induced cell death pathways in breast cancer subtypes.

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jason H. Winnike ◽  
Delisha A. Stewart ◽  
Wimal W. Pathmasiri ◽  
Susan L. McRitchie ◽  
Susan J. Sumner

Purpose. To conduct an exploratory study to identify mechanisms that differentiate Luminal A (BT474 and MCF-7) and triple-negative (MDA-MB-231 and MDA-MB-468) breast cancer (BCa) cell lines to potentially provide novel therapeutic targets based on differences in energy utilization. Methods. Cells were cultured in media containing either [U-13C]-glucose or [U-13C]-glutamine for 48 hours. Conditioned media and cellular extracts were analyzed by 1H and 13C NMR spectroscopy. Results. MCF-7 cells consumed the most glucose, producing the most lactate, demonstrating the greatest Warburg effect-associated energy utilization. BT474 cells had the highest tricarboxylic acid cycle (TCA) activity. The majority of energy utilization patterns in MCF-7 cells were more similar to MDA-MB-468 cells, while the patterns for BT474 cells were more similar to MDA-MB-231 cells. Compared to the Luminal A cell lines, TNBC cell lines consumed more glutamine and less glucose. BT474 and MDA-MB-468 cells produced high amounts of 13C-glycine from media [U-13C]-glucose which was integrated into glutathione, indicating de novo synthesis. Conclusions. Stable isotopic resolved metabolomics using 13C substrates provided mechanistic information about energy utilization that was difficult to interpret using 1H data alone. Overall, cell lines that have different hormone receptor status have different energy utilization requirements, even if they are classified by the same clinical BCa subtype; and these differences offer clues about optimizing treatment strategies.


Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1239 ◽  
Author(s):  
Rajeev Vikram ◽  
Wen Cheng Chou ◽  
Shih-Chieh Hung ◽  
Chen-Yang Shen

Cells with high CD44 but low CD24 expression (CD44high/CD24−/low) and high aldehyde dehydrogenase activity (ALDHbr) are widely considered to be drivers of metastasis, therapy resistance and tumor recurrence in breast cancer. However, the role of the CD44high/CD24−/low and ALDHbr phenotypes in identifying tumorigenic cells in breast cancer remains controversial due to the discrepancy in their distribution and tumorigenic potential in intrinsic breast cancer subtypes. In this study, we analyzed the cells expressing these markers in six different breast cancer cell lines representing major breast cancer subtypes (T47D, MCF-7, BT-474, AU-565, Hs578T and MDA-MB-231). CD44high/CD24−/low, ALDHbr and CD44−/low/CD24−/low cell populations were isolated by flow cytometry and analyzed for hallmark stem cell characteristics of differentiation, migration, invasiveness and metastasis using in vitro and in vivo techniques. Our results demonstrate that the CD44−/low/CD24−/low cell population, which is enriched in luminal cell lines (T47D, MCF-7 and BT-474), possesses metastatic and tumorigenic properties. We also show that, contrary to previous claims, the expression of the ALDH1 isoform ALDH1A1 does not affect the tumorigenic potential of cell lines with high ALDH activity (BT-474 and AU-565). Further transcriptomic and clinical studies are needed to determine the potential of these markers as early diagnostic tools and treatment targets.


Breast Cancer ◽  
2019 ◽  
Vol 27 (2) ◽  
pp. 225-235
Author(s):  
Shinsuke Miyazawa ◽  
Shota Moriya ◽  
Hiroko Kokuba ◽  
Hirotsugu Hino ◽  
Naoharu Takano ◽  
...  

2019 ◽  
Vol 8 (2) ◽  
pp. 101-106
Author(s):  
Amin Mohammadi ◽  
Ali Mostafaie ◽  
Ahmad Bagheri ◽  
Sarah Kiani ◽  
Maryam Chalabi

Background: Breast cancer is the most common cause of cancer-related death in women worldwide. Therefore, there is an urget need to identify and develop therapeutic strategies against this deadly disease. This study is the first to investigate the effects of Hemolymph Serum of Potamon persicum Crab (HSPPC) on MCF-7 and MDA-231 breast cancer cell lines. Materials and Methods: LDH and MTT assays were performed on MCF-7 and MDA-231 breast cancer cell lines as well as human umbilical vein endothelial cells (HUVEC) to determine the cytotoxic and antiproliferative activity of the HSPPC at different concentrations. Further, the apoptosis inducing action of the hemolymph serum was determined by TUNEL (terminal deoxynucleotidyl transferasemediated dUTP nick end labeling) and cell death assay. Results: The IC50 values of HSPPC for MCF-7 and MDA-231 cell lines were 960±0.369 and 850±1.422 μg/mL, respectively. The growth of both MCF-7 and MDA-231 cell lines were significantly (P<0.001) inhibited by HSPPC as compared with untreated controls at 48 hours. The results showed that HSPPC had no cytotoxic effects but significantly inhibited cell growth in a dose and time dependent manner. In addition, DNA fragmentation analysis (TUNEL) and cell death assay indicated induction of apoptosis by HSPPC in MCF-7 and MDA-231 cell lines. Conclusion: The results suggest that HSPPC contains bioactive compound(s) with potentials for the treatment of breast cancer.


Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5325
Author(s):  
Mami Kurosaki ◽  
Mineko Terao ◽  
Dawei Liu ◽  
Adriana Zanetti ◽  
Luca Guarrera ◽  
...  

Circular RNAs are regulatory molecules involved in numerous cellular processes and may be involved in tumour growth and diffusion. Here, we define the expression of 15 selected circular RNAs, which may control the process of epithelial-to-mesenchymal transition, using a panel of 18 breast cancer cell lines recapitulating the heterogeneity of these tumours and consisting of three groups according to the mesenchymal/epithelial phenotype. A circular RNA from the DOCK1 gene (hsa_circ_0020397) shows low/undetectable levels in triple-negative mesenchymal cell lines, while its content is high in epithelial cell lines, independent of estrogen receptor or HER2 positivity. RNA-sequencing experiments performed on the triple-negative/mesenchymal MDA-MB-231 and MDA-MB-157 cell lines engineered to overexpress hsa_circ_0020397 demonstrate that the circRNA influences the expression of 110 common genes. Pathway analysis of these genes indicates that overexpression of the circular RNA differentiates the two mesenchymal cell lines along the epithelial pathway and increases cell-to-cell adhesion. This is accompanied by growth inhibition and a reduction in the random/directional motility of the cell lines. The upregulated AGR2, ENPP1, and PPP1R9A genes as well as the downregulated APOE, AQP3, CD99L2, and IGFBP4 genes show an opposite regulation by hsa_circ_0020397 silencing in luminal CAMA1 cells. The results provide novel insights into the role played by specific circular RNAs in the generation/progression of breast cancer.


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