scholarly journals The connection of miR-21 and miR-155 with regulation of 15-HPGDH mRNA in human breast cancer cells

2016 ◽  
Vol 62 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Z.N. Nikiforova ◽  
M.A. Taipov ◽  
I.A. Kudryavcev ◽  
V.E. Shevchenko

Breast cancer is the most frequent cancer and the leading cause of cancer-related deaths in women worldwide. We determined the expression of COX2, COX1, 15-HPGDH mRNA and miRNAs (miR-21, miR-155) in three estrogen positive human breast cancer cell lines (MCF-7, BT-474, ZR-75-1). According to the results of three independent experiments the amount of COX1 and COX2 mRNA was significantly higher in the ZR-75-1 than in MCF-7 and BT-474 cells. Levels of total 15-HPGDH; functional 15-HPGDH mRNA in BT-474 cell line were lower than in MCF-7 and ZR-75-1 ones. The synthesis of 15-HPGDH enzyme in BT-474 line was blocked at the nuclear immature pre-mRNA processing level. miR-155 expression level was significantly lower than miR-21 in breast cancer cell lines. Correlations between the dysregulation of miR-21, miR-155 and 15-HPGDH, COX-1, COX-2 mRNA were identified. Expression of miR-21 was high in MCF-7, ZR-75-1 and BT-474 cell lines. Our results show that miR-21 and miR-155 regulate activity of several genes in cancer cells, their effect on the individual genes was in some cases cumulative. Based on our results, we concluded that miR-21, miR-155 suppress the work of tumor suppressor gene 15-HPGDH and induce potential oncogene COX-2 that promotes cell malignancy and metastasis of breast cancer.

Author(s):  
Nadjiba Zegheb ◽  
Cherifa Boubekri ◽  
Touhami Lanez ◽  
Elhafnaoui Lanez ◽  
Tuba Tüylü Küçükkılınç ◽  
...  

Background: Since the binding of estradiol to its receptor promotes breast cancer cell proliferation (in the ER+ tumours), many molecules targeting this protein have been synthesized to counteract the estradiol action. Ferrocene derivatives have proved their efficiency against hormone-dependent breast cancer cells (MCF-7). Objective: In this study, we aimed to find new ferrocene derivatives having pharmacochemistry properties as potential drugs against human breast cancer cells. Methods: A series of 29 N-ferrocenylmethylaniline derivatives A0-A28 were synthesised, and their anti-proliferative activity against both hormone-dependent (MCF-7) and independent (MDA-MB 231) human breast cancer cell lines were performed using the MTT test. Molecular docking and drug-likeness prediction were also performed for the five most active derivatives towards MCF-7. A QSAR model was also developed for the perdition of the anti-proliferative activity against MCF-7 cell lines using molecular descriptors and MLR analysis. Results: All studied derivatives demonstrated better cytotoxicity against MCF-7 compared to the MDA-MB-231 cell lines, and compounds A2, A9, A14, A17, and A27 were the most potent ones; however, but still less active than the standard anti-cancer drug crizotinib. The QSAR study revealed good predictive ability as shown by R2cv = 0.848. Conclusion: In vitro and in silico results indicated that derivatives A2, A9, A14, A17, and A27 possess the highest anti-proliferative activity, t. These results can be used to design more potent N-ferrocenylmethylaniline derivatives as anti-proliferative agents.


Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3218 ◽  
Author(s):  
Fu Peng ◽  
Huan Zhu ◽  
Chun-Wang Meng ◽  
Yan-Rui Ren ◽  
Ou Dai ◽  
...  

The rattans of Spatholobus suberectus Dunn are a traditional Chinese medicine activating blood circulation and removing stasis. They have often been used for the traditional Chinese medicinal treatment of breast cancer in modern China. In this study, four novel isoflavanes (1–3 and 5) and four known analogues (4 and 6–8) were isolated from an ethanolic extract of the rattans of S. suberectus. Their structures were elucidated by extensive spectroscopic analyses and electronic circular dichroism studies. MCF-7 and MDA-MB-231 human breast cancer cell lines were used to evaluate the cytotoxic effects of the isolates. Interestingly, compounds 1 and 2 only inhibited the proliferation of MCF-7 cells, while compound 6 showed a selective cytotoxicity against MDA-MB-231 cells. However, compound 4 had significant cytotoxicity against both MCF-7 and MDA-MB-231 cell lines.


1981 ◽  
Vol 196 (2) ◽  
pp. 513-520 ◽  
Author(s):  
D M Findlay ◽  
V P Michelangeli ◽  
J M Moseley ◽  
T J Martin

Two human breast cancer cell lines (MCF 7 and T 47D) possess calcitonin-responsive adenylate cyclase systems. Suspended cells of both lines specifically bound 125I-labelled salmon calcitonin with mean dissociation constants of 1.7 nM (MCF 7) and 1.4 nM (T 47D); mean receptor numbers were 5300 and 24400 per cell respectively. Measurement of specific binding to MCF 7 cells was obscured by rapid and substantial degradation of the labelled hormone. Degradation of 125I-labelled salmon calcitonin: (i) was of high capacity; (ii) lacked the specificity displayed by 125I-labelled salmon calcitonin binding to the same cells; and (iii) was not related to binding since cell incubation supernatants retained full degrading activity. The degrading activity was inhibited by corticotropin (1-24)-tetracosapeptide, insulin and bacitracin. Inclusion of bacitracin in the incubation resulted in apparently fewer numbers of lower affinity receptors on MCF 7 cells, whereas these parameters were identical to T 47D cells incubated in the presence or absence of bacitracin. Eel [2-aminosuberic acid 1,7]-calcitonin was resistant to proteolysis in the presence of either cell line. Analysis of hormone-receptor interactions with calcitonin-responsive cells should take account of potent calcitonin-degrading activities in some cell lines.


Author(s):  
Hadi Kalantar ◽  
Masoumeh Sabetkasaei ◽  
Ali Shahriari ◽  
Mostafa Haj Molla Hoseini ◽  
Siavash Mansouri ◽  
...  

2020 ◽  
Vol 20 (16) ◽  
pp. 1499-1503
Author(s):  
Hua Guo ◽  
Quan-Ping Diao

Aims: To develop novel anti-breast cancer agents and discuss the structure-activity relationship of bis-isatin scaffolds. Background: Breast cancer is the most common invasive cancer and the second leading cause of cancer death in women after lung cancer. Bis-isatin scaffolds possess potential anti-breast cancer activity, and some of them such as Indirubin could induce cancer cells apoptosis via multiply mechanisms. Objective: The primary objective of this study was to evaluate the potential of bis-isatin scaffolds with alkyl/ether linkers between the two isatin moieties against different human breast cancer cell lines including MCF-7, AU565, MDA-MB-231, MDA-MB-435 and MDA-MB-468 cells. Methods: The synthesized bis-isatin scaffolds with alkyl/ether linker between the two isatin moieties were evaluated for their in vitro activity against MCF-7, AU565, MDA-MB-231, MDA-MB-435, and MDA-MB-468 human breast cancer cell lines by MTT assay. Result: All the synthesized compounds (IC50: 38.3-197.6 µM) possess considerable activity against MCF-7, AU565, MDA-MB-231, MDA-MB-435, and MDA-MB-468 human breast cancer cell lines, and the most potent compound 4e (IC50: 38.3-63.5 µM) was no inferior to Cisplatin (IC50: 20.1-38.6 μM) against the five tested human breast cancer cell lines. Conclusion: All the synthesized bis-isatin scaffolds were active against a panel of breast cancer cell lines, highlighting the significance of exploring the bis-isatin scaffolds to fight against breast cancers. The enriched structure-activity relationship may set up the direction for the rational design and development of novel bis-isatin scaffolds with higher efficiency.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11506-11506
Author(s):  
R. Hass ◽  
H. Lueck ◽  
R. von Wasielewski ◽  
H. Jin ◽  
A. Pich ◽  
...  

11506 Background: A novel technique to obtain individual primary cultures of human breast cancer biopsies was filed for patent (PCT/DE 2006/000608). The different individualized HBCEC (human breast cancer epithelial cell) cultures will be characterized and chemotherapeutic effects will be compared to established breast cancer cell lines. Methods: Primary HBCEC from 20 different breast cancer patients were characterized for epithelial cell and tumor markers by immunofluorescence and PCR. Following treatment with 1μM epirubicin for 1h up to 72h differences in protein expression patterns were compared to the similarly treated MCF-7 cell line by 2D gel electrophoresis. Differentially expressed protein spots were identified by mass spectrometry and confirmed by appropriate Western blot analysis. Results: Characterization of primary HBCEC revealed continuous mitosis and cell cycle progression for more than one year in culture with no significant contamination by fibroblasts or other cell types. Whereby HBCEC underwent cell death within 72h of epirubicin treatment analysis by 2D gel and subsequent protein identification by MALDI-TOF/TOF mass spectrometry exhibited a variety of differences compared to MCF-7 cells including HSP27 and prohibitin. Appropriate Western blots confirmed these differences and revealed altered expression levels for HSP27 and prohibitin in the course of epirubicin exposure in HBCEC and MCF-7 cells, respectively, suggesting altered signalling pathways in either primary breast cancer cells or the tumor cell line. Conclusions: Individualized primary HBCEC from various patients could provide a cellular platform beyond breast cancer cell lines, which eventually meet the requirements for an appropriate breast cancer testing system including the characterization of biomarkers and the identification of potential molecular targets. No significant financial relationships to disclose.


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