Obese adipose tissue extracellular vesicles raise breast cancer cell malignancy

2020 ◽  
Vol 27 (10) ◽  
pp. 571-582 ◽  
Author(s):  
Isadora Ramos-Andrade ◽  
João Moraes ◽  
Renata Machado Brandão-Costa ◽  
Simone Vargas da Silva ◽  
Antônio de Souza ◽  
...  

Obesity is a chronic low-grade inflammatory condition that strongly impacts breast cancer. Aside from inflammatory mediators, obese adipose tissue (AT) secretes high amounts of extracellular vesicles (EVs), which are capable of transferring molecules to target cells and promoting cell-to-cell communication. Here, we investigated how soluble mediators and EVs secreted by human obese AT influence MCF-7 and MDA-MB-231 mammary adenocarcinoma cell lines by modulating cell proliferation, migration, invasion, and signaling pathways. Both cell lineages were stimulated with conditioned media (CM) or EVs obtained from cultures of AT explants collected from lean or obese individuals who underwent plastic or bariatric surgeries, respectively. EVs derived from obese AT increased the proliferative potential of both cell lines and further potentiated the migratory and invasive properties of MDA-MB-231 cells. The proliferative effects of CM and EVs on MCF-7 cells were dependent on ERK/MAPK pathway activation, while the migration and invasiveness of MDA-MB-231 cells were dependent on PI3K/AKT pathway activation. Furthermore, CM derived from obese AT potentiated the pro-angiogenic effect of MDA-MB-231 on endothelial cells. We also detected that EVs derived from obese AT were enriched in leptin and bioactive matrix metallopeptidase 9 (MMP9), and stimulation of MDA-MD-231 cells with those EVs or CM derived from obese AT potentiated the release of MMP9 by those cells. Our data indicate that obese AT secretes molecules and EVs with pro-tumoral activities capable of increasing breast cancer cell malignancy and provide strong evidence of the key role of AT-derived EV signaling in the tumor microenvironment.

2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity


2000 ◽  
Vol 2 (S1) ◽  
Author(s):  
CJ Pogson ◽  
CMW Chan ◽  
L-A Martin ◽  
GPH Gui ◽  
M Dowsett

Author(s):  
Muhammad Luqman Nordin ◽  
Arifah Abdul Kadir ◽  
Zainul Amiruddin Zakaria ◽  
Rasedee Abdullah ◽  
Muhammad Nazrul Hakim Abdullah

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5577 ◽  
Author(s):  
Mohadeseh Hasanpourghadi ◽  
Nazia Abdul Majid ◽  
Mohd Rais Mustafa

Combination Index (CI) analysis suggested that MBIC and doxorubicin synergistically inhibited up to 97% of cell proliferation in ER+/PR+MCF-7 and triple negative MDA-MB-231 breast cancer cell lines. Moreover, treatment of the breast cancer cells with the combined drugs resulted in lower IC50 values in contrast to the individual drug treatment. Small noncoding microRNAs (miRNA) may function as non-mutational gene regulators at post-transcriptional level of protein synthesis. In the present study, the effect of the combined treatment of MBIC and doxorubicin on the expression level of several miRNAs including miR-34a, miR-146a, miR-320a and miR-542 were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. These miRNAs have the potential to alter the protein level of survivin, the anti-apoptotic protein and reduce the metastatic activity in human breast cancer cell lines by interfering with the nuclear accumulation of NF-κB. Our results demonstrated the several fold changes in expression of miRNAs, which is drug and cell line dependent. This finding demonstrated a functional synergistic network between miR-34a, miR-320a and miR-542 that are negatively involved in post-transcriptional regulation of survivin in MCF-7 cells. While in MDA-MB-231 cells, changes in expression level of miR-146a was correlated with inhibition of the nuclear translocation of NF-κB. The overall result suggested that alteration in protein level and location of survivin and NF-κB by miR-34a, miR-320a, miR-146a and miR-542, remarkably influenced the synergistic enhancement of combined MBIC and doxorubicin in treatment of aggressive and less aggressive human breast cancer cell lines.


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.


2018 ◽  
Vol 500 (4) ◽  
pp. 860-865 ◽  
Author(s):  
Fahimeh Aghapour ◽  
Ali Akbar Moghadamnia ◽  
Andrea Nicolini ◽  
Seydeh Narges Mousavi Kani ◽  
Ladan Barari ◽  
...  

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