scholarly journals Incorporation of Functionalized Calcium Phosphate Nanoparticles in Living Cells

Author(s):  
Manuel Rivas ◽  
Pau Turon ◽  
Carlos Alemán ◽  
Jordi Puiggalí ◽  
Luis J. del Valle

AbstractIntracellular calcium (Ca2+) is a key signaling element that is involved in a great variety of fundamental biological processes. Thus, Ca2+ deregulation would be involved in the cancer cell progression and damage of mitochondrial membrane and DNA, which lead to apoptosis and necrosis. In this study, we have prepared amorphous calcium phosphate nanoparticles (ACP NPs) for studied their incorporation by endocytosis or electroporation to epithelial, endothelial and fibroblast cells (MCF-7, HUVEC and COS-1 cells, respectively). Our results showed that internalized ACP NPs have cytotoxic effects as a consequence of the increase of the intracellular calcium content. The endocytosis pathways showed a greater cytotoxic effect since calcium ions could easily be released from the nanoparticles and be accumulated in the lysosomes and mitochondria. In addition, the cytotoxic effect could be reversed when calcium ion was chelated with ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid (EGTA). Modification of ACP NPs by coating with different compounds based on phosphates was also evaluated. The results indicated a reduction of the cytotoxic effect, in the order polyphosphate < phosphonic acid < orthophosphate. A differential cytotoxic effect of ACP-NPs was observed in function of the cell type; the cytotoxic effect can be ordered as i.e., HUVEC > COS-1 > MCF-7. The greater cytotoxic effect caused by the increase of intracellular calcium that is observed in normal cells and the greater resistance of cancer cells suggests new perspectives for cancer research.

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e97565 ◽  
Author(s):  
Yana Dautova ◽  
Diana Kozlova ◽  
Jeremy N. Skepper ◽  
Matthias Epple ◽  
Martin D. Bootman ◽  
...  

2010 ◽  
Vol 441 ◽  
pp. 299-305 ◽  
Author(s):  
Matthias Epple ◽  
Anna Kovtun

Calcium phosphate is a natural biomineral and therefore possesses an excellent biocompatibility due to its chemical similarity to human hard tissue (bone and teeth). Calcium phosphate nanoparticles can be precipitated under controlled conditions and used as carrier in biological systems, e.g. to transfer nucleic acids or drugs. Such nanoparticles can also be suitably functionalized with fluorescing dyes, polymeric agents, pro-drugs or activators. The small monodisperse nanoparticles only mildly influence the intracellular calcium level and therefore are not toxic for cells.


Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 671
Author(s):  
Gözde Koygun ◽  
Emine Arslan ◽  
Gökhan Zengin ◽  
Giustino Orlando ◽  
Claudio Ferrante

Dorycnium pentaphyllum subsp. haussknechtii is an important medicinal plant in several countries, including Turkey. This study aimed to evaluate the cytotoxicity of a crude extract of D. pentaphyllum subsp. haussknechtii against different breast cell lines to determine invasion, adhesion, and lipid peroxidation. The cytotoxic effects on MCF-7 breast cancer and MCF-12A as the immortalized cell line were examined by the XTT assay. Invasion and adhesion studies were performed according to the manufacturer’s kit procedure to IC50 values for 48 h. Lipid peroxidation was measured in the MCF-7 cell. A bioinformatics analysis was conducted to unravel the mechanism of action underlying antiproliferative effects, as well. According to XTT results, the tested extract showed a time- and a concentration-dependent cytotoxic effect. The most effective concentration was 100.5 µg/mL (48 h), which was selected for biological activities, such as apoptotic activity, invasion, adhesion, and lipid peroxidation assays. The extract caused tumoral cell death, and it did not have a cytotoxic effect on healthy human breast cells. Duplication times and measurement of CI analyses of cells were performed using the real-time cell analysis system xCELLigence. Finally, the bioinformatics analysis indicated the prominent role of quercetin as an extract component exerting a key role in the observed antiproliferative effects. This was supported by the micromolar/submicromolar affinity of quercetin towards proto-oncogene serine/threonine–protein kinase (PIM-1) and hematopoietic cell kinase (HCK), both involved in breast cancer. Altogether, our findings proposed that the extraction of the plant can be an effective strategy to isolate biomolecules with promising cytotoxic effects against breast cancer cells.


Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3045 ◽  
Author(s):  
Marta Hałas-Wiśniewska ◽  
Wioletta Zielińska ◽  
Magdalena Izdebska ◽  
Alina Grzanka

Background: Cancers are one of the leading causes of deaths nowadays. The development of new treatment schemes for oncological diseases is an interesting direction in experimental medicine. Therefore, the evaluation of the influence of two alkaloids—piperlongumine (PL), sanguinarine (SAN) and their combination—on the basic life processes of the A549 cell line was considered reasonable. Methods: The aim was achieved by analyzing the cytotoxic effects of PL and SAN and their combination in the ratio of 4:1 on the induction of cell death, changes in the distribution of cell cycle phases, reorganization of cytoskeleton and metastatic potential of A549 cells. The versatility of the applied concentration ratio was evaluated in terms of other cancer cell lines: MCF-7, H1299 and HepG2. Results: The results obtained from the MTT assay indicated that the interaction between the alkaloids depends on the concentration and type of cells. Additionally, the compounds and their combination did not exhibit a cytotoxic effect against normal cells. The combined effects of PL and SAN increased apoptosis and favored metastasis inhibition. Conclusion: Selected alkaloids exhibit a cytotoxic effect on A549 cells. In turn, treatment with the combination of PL and SAN in a 4:1 ratio indicates a synergistic effect and is associated with an increase in the level of reactive oxygen species (ROS).


Biomaterials ◽  
2009 ◽  
Vol 30 (35) ◽  
pp. 6794-6802 ◽  
Author(s):  
Sebastian Neumann ◽  
Anna Kovtun ◽  
Irmgard D. Dietzel ◽  
Matthias Epple ◽  
Rolf Heumann

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1565
Author(s):  
Asli Aykac ◽  
Eda Becer ◽  
Tuğçe Balcı Okcanoğlu ◽  
Meryem Güvenir ◽  
Kaya Süer ◽  
...  

Breast cancer is the most common cancer among women and in order to create alternative treatments different types of in vivo and in vitro studies have used various plant-based therapeutic agents. Humic acid (HA) induces apoptosis and has various pharmacological properties including anti-inflammatory and anti-proliferative effects. In our study, we examined the cytotoxic effects of HA at concentrations of 5, 10, 20, 50 and 100 μg/mL in human breast adenocarcinoma MCF-7 cell line for 24 and 48 h. By using MTT method, it has been found out that HA 100 g/mL had cytotoxic effect on human breast adenocarcinoma MCF-7 cell line at both 24 and 48 h; also found out that the effective dose of HA at the same time (24 and 48 h) was 50 μg/mL. The results of our study will shed light on the development of alternative therapeutic approaches in the treatment of cancer by evaluating the cytotoxic effect of HA.


Author(s):  
K. A. Luneva ◽  
K. E. Ternovskaya ◽  
O. E. Klement’eva ◽  
A. S. Lunev

The radiopharmaceutical precursor «Oxind, 111In» is a complex compound for labeling autologous leukocytes of human blood and their subsequent introduction for non-specific visualization and localization of inflammation foci of different nature by single-photon emission computed tomography (SPECT). The cytotoxic effect of lyophilisate for preparation of radiopharmaceutical preparation «Oxind, 111In» and its radiopharmaceutical precursor on rabbit blood leukocytes has been investigated. In the course of studies of the cytotoxicity of the lyophilisate for the preparation of a radiopharmaceutical precursor with successively increasing concentrations of the main substance, 8-hydroxyquinoline, the permissible concentrations have been determined and the absolutely cytotoxic concentration was achieved.In the study of the cytotoxic effect of the precursor of radiopharmaceutical on two dosages that differ by 10 times in volume activities (MBq / ml), the absence of cytotoxic effects has been confirmed.


Author(s):  
Zeinab Abedian ◽  
Niloofar Jenabian ◽  
Ali Akbar Moghadamnia ◽  
Ebrahim Zabihi ◽  
Roghayeh Pourbagher ◽  
...  

Objective/ Background: Cancer is still the most common cause of morbidity in world and new powerful anticancer agents without severe side effects from natural sources is important. Methods: The evaluation of cytotoxicity and apoptosis induction was carried out in MCF-7,HeLa and Saos-2 as cancerous cell lines with different histological origin and human fibroblast served as control normal cell. The cells were treated with different concentrations of chitosan and the cytotoxicity was determined using MTT assay after 24, 48 and 72 h .The mode of death was evaluated by flow cytometry . Results: While both types of chitosan showed significant concentration-dependently cytotoxic effects against the three cancerous cell lines, fibroblast cells showed somehow more compatibility with chitosan. On the other hand, there were no significant differences between LMWC and HMWC cytotoxicity in all cell lines. The flow cytometry results showed the apoptosis pattern of death more in Saos-2 and HeLa while necrosis was more observable with MCF7. Also higher viability with both types of chitosan was seen in fibroblast as normal cells Conclusion: Chitosan shows anticancerous effect against 3 cancerous cell lines, while it is compatible with normal diploid fibroblast cells. Furthermore, it seems that the molecular weight of chitosan does not affect its anticancerous property.


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