scholarly journals Anti-Cancer Activity of Gabapentin and Chiral Amino Acids-Based Hybrid-Peptides against MCF-7 Breast Cancer Cell-Line

Author(s):  
Vraj B. Pansuriya ◽  
Khushal M. Kapadiya ◽  
Suryajitsinji L. Rathod ◽  
Usha B. Prajapati ◽  
Bhavin M. Vavaiya ◽  
...  

Aims: Herein, we report the cytotoxicity of gabapentin-based peptides (11a-11j) using L-alanine and L-phenyl alanine chiral amino acids for peptide bond formation in ten efficient and straightforward steps. The in vitro MTT assays of derived molecules on the MCF-7 cell line (a human breast adenocarcinoma cell line) exhibited enhanced antitumor activity compared to the control (100% cell proliferation). Methods: The ten steps synthetic methods were adapted for the synthesis of the Gabapentin-based peptide derivatives through BOC- deBOC methods and using EDC-HCl, DMAP and commercially available solvents. All the synthesized peptides were unambiguously characterized with the help of spectroscopic (IR, 1H NMR, 13C-NMR, mass spectra, and elemental) data analysis. Results: The Compounds 11a, 11b, 11h,11i, and 11j showed a remarkable antiproliferative (cell death) activity, with % cell proliferation values ranging from 25-38 %. Conclusion: The study showed that the compounds with some specific functionalities like, benzylic and trifluoromethyl functionality enhanced the potency with comparable %cell proliferation and cell death. Based on the findings in this work and their easily accessible molecular structures, compounds 11a and 11j are worthy of further biological investigations.

2019 ◽  
Vol 45 (3) ◽  
pp. 295-304
Author(s):  
Nail Besli ◽  
Guven Yenmis ◽  
Matem Tunçdemir ◽  
Elif Yaprak Sarac ◽  
Sibel Doğan ◽  
...  

AbstractObjectiveMCF-7 cells, a breast cancer cell line, are used for experiments of estrogen receptor (ER)-positive breast cancer and many sub-clones representing different classes of ER-positive tumors. We aimed to determine the efficacy of metformin, a potential anti-cancer agent, on the cell proliferation, and the expressions of NF-kB (p65), MMP-2 and MMP-9 in MCF-7 cell line.Materials and methodsMCF-7 cells (human breast adenocarcinoma) were treated with elevating doses of metformin (0–50 mM) for 24 h. The anti-proliferative effect of metformin was studied by BrdU proliferation assay, and the expression levels of NF-kB (p65), MMP-2 and MMP-9 were analyzed by immunocytochemical staining.ResultsThe percentage of cell proliferation was reduced significantly by 10 and 50 mM doses of metformin (p < 0.001). The expression levels of nuclear NF-kB (p65), MMP-9 and MMP-2 were considerably reduced in 50 mM metformin treated cells while the expression of cytoplasmic NF-kB (p65) elevated compared to control group (p < 0.05). Ten millimolar metformin also reduced expression of MMP-9 significantly (p < 0.05).ConclusionMetformin may act on the proliferation, and the processes of invasion and metastasis of MCF-7 cells through blocking NF-kB, which is intensely expressed in breast cancer cells, and through diminishing the expression of MMP-2 and MMP-9 significantly.


2002 ◽  
Vol 173 (1) ◽  
pp. 161-167 ◽  
Author(s):  
C Gil-Puig ◽  
M Blanco ◽  
T Garcia-Caballero ◽  
C Segura ◽  
R Perez-Fernandez

GH expression in mammary tumors has been related to the increase and spreading of cell proliferation. Using the MCF-7 human breast adenocarcinoma cell line, it has been demonstrated that autocrine GH-stimulated mammary carcinoma cell proliferation decreased the apoptosis rate and enhanced cell spreading. Surprisingly, no data are available about the presence of Pit-1 (the main pituitary regulator of GH) or GH expression in this cell line. Using RT-PCR, Western blot and immunohistochemistry, we have demonstrated the presence of both mRNA coding Pit-1 and GH as well as Pit-1 and GH protein in the MCF-7 cell line. These data could imply that Pit-1 may be an adequate target to inhibit breast cell proliferation.


Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1240
Author(s):  
Asvinidevi Arumugam ◽  
Muhammad Din Ibrahim ◽  
Saie Brindha Kntayya ◽  
Nooraini Mohd Ain ◽  
Renato Iori ◽  
...  

Gluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the study is to evaluate the cytotoxicity of GNST-ITC and to further assess its potential to induce apoptosis. GNST-ITC inhibited cell proliferation in both human hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7) cells with IC50 values of 7.83 µM and 5.02 µM, respectively. Morphological changes as a result of GNST-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GNST-ITC in a time-dependent manner. To delineate the mechanism of apoptosis, cell cycle arrest and expression of caspases were studied. GNST-ITC induced a time-dependent G2/M phase arrest, with reduction of 82% and 93% in HepG2 and MCF-7 cell lines, respectively. The same treatment also led to the subsequent expression of caspase-3/7 and -9 in both cells demonstrating mitochondrial-associated cell death. Collectively, these results reveal that GNST-ITC can inhibit cell proliferation and can induce cell death in HepG2 and MCF-7 cancer cells via apoptosis, highlighting its potential development as an anticancer agent.


2020 ◽  
Vol 15 (1) ◽  
pp. 49-58
Author(s):  
Junhe Zhang ◽  
Shujie Chai ◽  
Xinyu Ruan

Background: Breast cancer is among the most common malignant cancers worldwide, and breast adenocarcinoma in glandular tissue cells has excessive metastasis and invasion capability. However, little is known on the molecular process by which this disease develops and progresses. Objective: In this study, we explored the effects of sex-determining region Y-box 4 (SOX4) protein on proliferation, migration, apoptosis and tumourigenesis of breast adenocarcinoma and its possible mechanisms. Methods: The SOX4 overexpression or knockdown Michigan Cancer Foundation-7 (MCF-7) cell lines were established. Among the SOX4 overexpression or MCF-7 knockdown cell lines, proliferation, migration ability and apoptosis rate were detected. The expression levels of apoptosis-related proteins (Bax and Cleaved caspase-3) were analysed using Western blot. The effect of SOX4 on tumourigenesis was analysed using the clone formation assay in vitro and tumour xenograft experiment in nude mice. Results: Compared with the overexpression of control cells, proliferation and migration ability of SOX4 overexpression cells significantly increased, the apoptosis rate significantly decreased in addition to the expression levels of Bax and Cleaved caspase-3 (P < 0.05). Compared with the knockdown of control cells, proliferation and migration ability of SOX4 knockdown cells significantly decreased, and the apoptosis rate and expression levels of Bax and Cleaved caspase-3 significantly increased (P < 0.05). Clone formation and tumour growth abilities of SOX4 overexpression cells were significantly higher than those of the control cells (P < 0.05), whereas SOX4 knockdown cells had the opposite effect. Conclusion: SOX4 plays an oncogenic role in breast adenocarcinoma tumourigenesis by promoting cell proliferation, migration and inhibiting apoptosis. It can be used as a potential molecular target for breast cancer gene therapy.


2020 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  

Abstract Introduction: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated. Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex, flow cytometry and transwell assays were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively. Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a mediator on invasion and metastasis, and the tumor suppressor gene RUNX3. Conclusion: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers.


2020 ◽  
Vol 21 (3) ◽  
pp. 1090 ◽  
Author(s):  
Patrycja Bronowicka-Adamska ◽  
Anna Bentke ◽  
Małgorzata Lasota ◽  
Maria Wróbel

The S-Allyl-L-cysteine (SAC) component of aged garlic extract (AGE) is proven to have anticancer, antihepatotoxic, neuroprotective and neurotrophic properties. γ-Cystathionase (CTH), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (MPST) are involved in H2S/sulfane sulfur endogenous formation from L-cysteine. The aim of the study was to determine the effect of SAC on MCF-7 cells survival and apoptosis, which is a widely known approach to reduce the number of cancer cells. An additional goal of this paper was to investigate the effect of SAC on the activity and expression of enzymes involved in H2S production. The experiments were carried out in the human breast adenocarcinoma cell line MCF-7. Changes in the cell viability were determined by MTT assay. Cell survival was determined by flow cytometry (FC). Changes in enzymes expression were analyzed using Western blot. After 24 h and 48 h incubation with 2245 µM SAC, induction of late apoptosis was observed. A decrease in cell viability was observed with increasing SAC concentration and incubation time. SAC had no significant cytotoxic effect on the MCF-7 cells upon all analyzed concentrations. CTH, MPST and CBS expression were confirmed in non-treated MCF-7 cells. Significant decrease in MPST activity at 2245 µM SAC after 24 h and 48 h incubation vs. 1000 µM SAC was associated with decrease in sulfane sulfur levels. The presented results show promising SAC effects regarding the deterioration of the MCF-7 cells’ condition in reducing their viability through the downregulation of MPST expression and sulfate sulfur level reduction.


2013 ◽  
Vol 8 (4) ◽  
pp. 357-365
Author(s):  
Marianna Trebuňová ◽  
Galina Laputková ◽  
Imrich Géci ◽  
Igor Andrašina ◽  
Ján Sabo

AbstractThe aim of the study was to investigate the effect of high-frequency electromagnetic field of 900 MHz at 8 W input power on metabolic activity of human breast adenocarcinoma MCF-7 cells. With the aid of the colorimetric MTT assay, it was shown that there is significant change in cell culture survival exposed to docetaxel in field-free conditions in comparison with cells treated with docetaxel simultaneously exposed to high-frequency electromagnetic field.


2013 ◽  
Vol 32 (12) ◽  
pp. 699-707 ◽  
Author(s):  
Guoqing Zhao ◽  
Jun Guo ◽  
Dong Li ◽  
Chengyou Jia ◽  
Wanzhong Yin ◽  
...  

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