scholarly journals Phenotypic and microRNA transcriptomic profiling of the MDA-MB-231 spheroid-enriched CSCs with comparison of MCF-7 microRNA profiling dataset

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3551 ◽  
Author(s):  
Lily Boo ◽  
Wan Yong Ho ◽  
Norlaily Mohd Ali ◽  
Swee Keong Yeap ◽  
Huynh Ky ◽  
...  

Breast cancer spheroids have been widely used as in vitro models of cancer stem cells (CSCs), yet little is known about their phenotypic characteristics and microRNAs (miRNAs) expression profiles. The objectives of this research were to evaluate the phenotypic characteristics of MDA-MB-231 spheroid-enriched cells for their CSCs properties and also to determine their miRNAs expression profile. Similar to our previously published MCF-7 spheroid, MDA-MB-231 spheroid also showed typical CSCs characteristics namely self-renewability, expression of putative CSCs-related surface markers and enhancement of drug resistance. From the miRNA profile, miR-15b, miR-34a, miR-148a, miR-628 and miR-196b were shown to be involved in CSCs-associated signalling pathways in both models of spheroids, which highlights the involvement of these miRNAs in maintaining the CSCs features. In addition, unique clusters of miRNAs namely miR-205, miR-181a and miR-204 were found in basal-like spheroid whereas miR-125, miR-760, miR-30c and miR-136 were identified in luminal-like spheroid. Our results highlight the roles of miRNAs as well as novel perspectives of the relevant pathways underlying spheroid-enriched CSCs in breast cancer.

Homeopathy ◽  
2018 ◽  
Vol 107 (01) ◽  
pp. 032-039 ◽  
Author(s):  
Sinem Şeker ◽  
Celal Güven ◽  
Handan Akçakaya ◽  
Nurten Bahtiyar ◽  
Fahri Akbaş ◽  
...  

Background Gene expression analysis of cells treated with extreme dilutions or micro amounts of drugs has been used to provide useful suggestions about biological responses. However, most of the previous studies were performed on medicines being prepared from a variety of herbal and metal sources. This study investigated the effects of ultramolecular dilution of the taxane anti-cancer drugs, which are not commonly used in homeopathic medicines, on mRNA expression profiles of five key genes (p53, p21, COX-2, TUBB2A and TUBB3) in the breast cancer cell line MCF-7. Method MCF-7 cells were exposed to paclitaxel (Taxol) or docetaxel (Taxotere) preparations (6X, 5C and 15C dilutions prepared from pharmacological concentration of 25 nmol/L) for 72 hours. The cell culture groups were evaluated with the trypan blue dye exclusion method for the proliferation/cytotoxicity rates, immuno-staining β-tubulin for microtubule organization, and reverse transcription polymerase chain reaction for gene expression levels.Fold-change in gene expression was determined by the ΔΔCt method. Results The administration of diluted preparations had little or no cytotoxic effect on MCF-7 cells, but altered the expression of genes analyzed with a complex effect. According to the ΔΔCt method with a five-fold expression difference (p < 0.05) as a cut-off level, ultra-high dilutions of paclitaxel and docetaxel showed differential effects on the studied genes with a concentration-independent activity. Furthermore, the dilutions disrupted the microtubule structure of MCF-7 cells, suggesting that they retain their biological activity. Conclusion Despite some limitations, our findings demonstrate that gene expression alterations also occur with ultra-high dilutions of taxane drugs.


2019 ◽  
Vol 87 (3) ◽  
pp. 23 ◽  
Author(s):  
Julia Eichsteininger ◽  
Kerstin Kirisits ◽  
Claudia Smöch ◽  
Christa Stadlbauer ◽  
Chi Huu Nguyen ◽  
...  

We investigated the effect of 21 flavonoids in a three-dimensional in vitro system for their ability to inhibit gap formation by MCF-7 breast cancer spheroids in monolayers of lymphendothelial cells. Different representatives of the classes of flavones, flavonols, and flavanones were tested in the circular chemorepellent-induced defects (CCID)-assay. Bay11-7082, a known inhibitor of CCID formation served as the positive control. This study provides the first comparison of the potential of flavonoids to suppress features influencing the intravasation of MCF-7 breast cancer cells aggregates through the lymph endothelial barrier. The most significant effects were seen after incubation with the flavones luteolin, chrysin, and apigenin. Additional hydroxylation or methoxylation in positions 6 or 8, as expected, resulted in decreased activity. The tested flavanones remained without or low efficacy.


2020 ◽  
Vol 21 (14) ◽  
pp. 1528-1538
Author(s):  
Sarah Albogami ◽  
Hadeer Darwish ◽  
Hala M. Abdelmigid ◽  
Saqer Alotaibi ◽  
Ahmed Nour El-Deen ◽  
...  

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.


2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.


Author(s):  
G. Siva ◽  
S. Venkatesh ◽  
G. Prem Kumar ◽  
M. Muthukumar ◽  
T. Senthil Kumar ◽  
...  
Keyword(s):  

2021 ◽  
pp. 096032712110227
Author(s):  
S Kara-Ertekin ◽  
S Yazar ◽  
M Erkan

Pyrethroid pesticides are frequently used for household insect control of insects and in agriculture and livestock. Flumethrin is a pyrethroid that is used against ectoparasites in many animals. The goal of this study was to evaluate the cytotoxic, apoptotic, genotoxic, and estrogenic effects of flumethrin on the mammalian breast cancer cell line (MCF-7). Compared with control groups, a dose-dependent decrease was observed in cell viability at concentrations of 100 µM and higher. The cytotoxic and apoptotic effects detected by LDH assay and AO/EtBr staining increased significantly at a concentration of 1000 µM. The expression of BCL2, which is an anti-apoptotic gene, significantly decreased, whereas BAX, TP53, and P21 expression significantly increased. The results of a comet assay indicated that flumethrin significantly changed tail length, tail % DNA, tail moment, and Olive tail moment in concentrations above 1 and 10 µM. In addition, a 0.1 µM concentration of flumethrin affected ERα receptor mediated cell proliferation and increased transcription of estrogen-responsive pS2 (TFF1) and progesterone receptor (PGR) genes. As a result, flumethrin-induced apoptosis and cytotoxicity at a high concentration, while induced genotoxicity even at lower concentrations. Flumethrin is an endocrine disrupting insecticide with estrogenic effects at very low concentrations.


2021 ◽  
pp. 096032712199945
Author(s):  
AT Aliyev ◽  
S Ozcan-Sezer ◽  
A Akdemir ◽  
H Gurer-Orhan

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.


Coatings ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 6
Author(s):  
Sultan Alshehri ◽  
Syed Sarim Imam ◽  
Md Rizwanullah ◽  
Khalid Umar Fakhri ◽  
Mohd Moshahid Alam Rizvi ◽  
...  

In the present study, thymoquinone (TQ)-encapsulated chitosan- (CS)-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were formulated using the emulsion evaporation method. NPs were optimized by using 33-QbD approach for improved efficacy against breast cancer. The optimized thymoquinone loaded chitosan coated Poly (d,l-lactide-co-glycolide) nanoparticles (TQ-CS-PLGA-NPs) were successfully characterized by different in vitro and ex vivo experiments as well as evaluated for cytotoxicity in MDA-MB-231 and MCF-7 cell lines. The surface coating of PLGA-NPs was completed by CS coating and there were no significant changes in particle size and entrapment efficiency (EE) observed. The developed TQ-CS-PLGA-NPs showed particle size, polydispersibility index (PDI), and %EE in the range between 126.03–196.71 nm, 0.118–0.205, and 62.75%–92.17%. The high and prolonged TQ release rate was achieved from TQ-PLGA-NPs and TQ-CS-PLGA-NPs. The optimized TQ-CS-PLGA-NPs showed significantly higher mucoadhesion and intestinal permeation compared to uncoated TQ-PLGA-NPs and TQ suspension. Furthermore, TQ-CS-PLGA-NPs showed statistically enhanced antioxidant potential and cytotoxicity against MDA-MB-231 and MCF-7 cells compared to uncoated TQ-PLGA-NPs and pure TQ. On the basis of the above findings, it may be stated that chitosan-coated TQ-PLGA-NPs represent a great potential for breast cancer management.


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