scholarly journals CD44 Targeting Mediated by Polymeric Nanoparticles and Combination of Chlorine TPCS2a-PDT and Docetaxel-Chemotherapy for Efficient Killing of Breast Differentiated and Stem Cancer Cells In Vitro

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 278 ◽  
Author(s):  
Elisa Gaio ◽  
Claudia Conte ◽  
Diletta Esposito ◽  
Elena Reddi ◽  
Fabiana Quaglia ◽  
...  
Keyword(s):  
Polymeric Nanoparticles ◽  
Metastatic Potential ◽  
Mammosphere Formation ◽  
Formation Efficiency ◽  
First Time ◽  
Docetaxel Chemotherapy ◽  
Cd44 Targeting ◽  
Mcf 7 ◽  
Aldehyde Dehydrogenase Activity

The presence of rare but highly tumorigenic cancer stem cells (CSCs) within the tumors is recognized as one of the major reasons of failure of conventional chemotherapies, mainly attributed to the development of drug resistance and increasing metastatic potential. Here, we propose a therapeutic strategy based on the simultaneous delivery of docetaxel (DTX) and the photosensitizer meso-tetraphenyl chlorine disulfonate (TPCS2a) using hyaluronic acid (HA) coated polymeric nanoparticles (HA-NPs) for the targeting and killing of CD44 over-expressing breast cancer (BC) cells, both differentiated and CSCs (CD44high/CD24low population), thus combining chemotherapy and photodynamic therapy (PDT). Using the CD44high MDA-MB-231 and the CD44low MCF-7 cells, we demonstrated the occurrence of CD44-mediated uptake of HA-NPs both in monolayers and mammosphere cultures enriched in CSCs. Cell treatments showed that combination therapy using co-loaded NPs (HA@DTX/TPCS2a-NPs) had superior efficacy over monotherapies (HA@DTX-NPs or HA@TPCS2a-NPs) in reducing the self-renewal capacity, measured as mammosphere formation efficiency, and in eradicating the CSC population evaluated with aldehyde dehydrogenase activity assay and CD44/CD24 immunostaining. In summary, these in vitro studies demonstrated for the first time the potential of the combination of DTX-chemotherapy and TPCS2a-PDT for killing CSCs using properly designed NPs.

scholarly journals Mitotic arrest affects clustering of tumor cells

2021 ◽  
Author(s):  
Julia Bonnet ◽  
Lise Rigal ◽  
Odile Mondesert ◽  
Renaud Morin ◽  
Gaelle Corsaut ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Cell Aggregation ◽  
Metastatic Potential ◽  
Mitotic Arrest ◽  
Chemotherapeutic Agents ◽  
The Impact ◽  
Mcf 7

Abstract Background Cancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate CTC number or the size of CTC clusters. Results In this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we observed that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly and formed loose clusters. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact. Conclusions Altogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells.

scholarly journals Ochroborbone, A New Cytotoxic Indole Alkaloid from Ochrosia borbonica

2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200
Author(s):  
Yan-Ping Liu ◽  
A-Hong Chen ◽  
Ruo-Heng Li ◽  
Hui-Wen Yang ◽  
Hai-Nan Bao ◽  
...  
Keyword(s):  
Human Cancer ◽  
Indole Alkaloid ◽  
Spectroscopic Methods ◽  
Inhibitory Effects ◽  
Human Cancer Cell Lines ◽  
Stems And Leaves ◽  
Monoterpenoid Indole Alkaloid ◽  
First Time ◽  
Mcf 7

A new monoterpenoid indole alkaloid, ochroborbone (1), along with five known alkaloids (2–6), were isolated from the stems and leaves of Ochrosia borbonica. Among them, ochroborbone (1) is a rare C17-nor monoterpenoid indole alkaloid, and the known compounds (2-6) were isolated from Ochrosia for the first time. These structures were established on the basis of extensive spectroscopic methods. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1 and 2 exhibited inhibitory effects with IC50 values comparable with those of cisplatin.

Preparation of wormlike polymeric nanoparticles coated with silica for delivery of methotrexate and evaluation of anticancer activity against MCF7 cells

2017 ◽  
Vol 31 (9) ◽  
pp. 1305-1316 ◽  
Author(s):  
Farhad Gharebaghi ◽  
Naser Dalali ◽  
Ebrahim Ahmadi ◽  
Hossein Danafar
Keyword(s):  
Polymeric Nanoparticles ◽  
Drug Loading ◽  
Free Drug ◽  
Spherical Nanoparticles ◽  
Mcf7 Cells ◽  
Anti Cancer ◽  
The Impact ◽  
Cancer Activity ◽  
Mcf 7

Methotrexate is one of the most effective drugs that is commonly used in the treatment of cancer. However, its application is limited due to low solubility, high toxicity and rapid metabolism. Therefore, in the present study, worm-like polymeric nanoparticles as carrier of methotrexate were prepared using biodegradable copolymers (mPEG–PCL). The impact of nanoparticles’ geometry on the loading, delivery and drug’s anti-cancer activity was investigated. The di-block copolymer mPEG–PCL was being synthesized by a ring opening polymerization of ɛ-caprolactone in the presence of mPEG as the initiator and Sn(oct)2 as the catalyst. It was used for the preparation of worm-like micelles and coated with silica, so that their structures are stable after drying. The synthesized copolymers and nanoparticles were characterized by FTIR, HNMR, GPC, XRD, TGA, DLS, and FE-SEM analyses. The efficiencies of drug loading and release of nanoparticles as in vitro, was studied by high performance liquid chromatography. The MTT method was used to estimate the toxicity on MCF-7 cell category. The obtained results showed that the nanoparticles were worm-like particles with less than 150 nm diameter and about 1 µm length. The loading and encapsulation efficiencies of drug by the worm-like nanoparticles were 3.5 ± 0.14% and 65.6 ± 0.12%, respectively, while they were obtained as 2.1 ± 0.08% and 26 ± 0.10%, respectively, for spherical nanoparticles. The methotrexate diffusional behavior of worm-like nanoparticles was compared with that of the spherical ones. On the other hand, the anti-cancer activity of MTX-loaded nanoparticles was more than the free drug. The results of the MTT assay showed strong and dose-dependent inhibition of cell (MCF-7 category) growth by the nanoparticles compared with MTX. The inhibitory concentrations (IC50 i.e. reduction viability of cell to 50%) obtained for worm-like, spherical nanoparticles and free drug (incubation times 72 h) were 8.25 ± 0.20, 9.15 ± 0.17, 12.28 ± 0.15 µg/mL, respectively. It can be concluded that application of non-spherical nanoparticles is a better and more effective strategy for controlled and slow release of methotrexate in the treatment of cancer.

Generation of MCF-7 cells with aggressive metastatic potential in vitro and in vivo

2014 ◽  
Vol 148 (2) ◽  
pp. 269-277 ◽  
Author(s):  
Elke Ziegler ◽  
Marie-Therese Hansen ◽  
Maike Haase ◽  
Günter Emons ◽  
Carsten Gründker
Keyword(s):  
Metastatic Potential ◽  
Mcf 7

Deciphering of The Effect of Chemotherapeutic Agents on Human Glutathione S-Transferase Enzyme and MCF-7 Cell Line

2020 ◽  
Vol 27 (9) ◽  
pp. 888-894
Author(s):  
Havva Aybek ◽  
Yusuf Temel ◽  
Barzan Mirza Ahmed ◽  
Can Ali Ağca ◽  
Mehmet Çiftci
Keyword(s):  
Cell Line ◽  
Human Erythrocyte ◽  
Chemotherapeutic Agents ◽  
Cellular Viability ◽  
Ammonium Sulfate Precipitation ◽  
Glutathione S Transferase ◽  
In Vitro Effects ◽  
First Time ◽  
Mcf 7

Background: Cancer is the disease that causes the most death after cardiovascular diseases all over the world these days. Breast cancer is the most common type of cancer among women and ranks the second among cancer-related deaths after lung cancer. Chemotherapeutics act by killing cancer cells, preventing their spread and slowing their growth. Recent studies focus on the effects of chemotherapeutics on cancer cells and new chemotherapy approaches that targeting enzymes that catalyze important metabolic reactions in the cell. Objective: The aim of this study was to investigate the effects of chemotherapeutic agents, Tamoxifen and 5-FU, on MCF-7 cell line and human erythrocyte GST, an important enzyme of intracellular antioxidant metabolism. Methods: In this study, it was investigated that the effect of chemotherapeutic agents, Tamoxifen and 5-FU, on MCF-7 breast cancer cell line and performed ROS analyzes. In addition, it was purified glutathione S-transferase (GST), one of the important enzymes of intracellular antioxidant mechanism, from human erythrocytes by using ammonium sulfate precipitation and glutathione agarose affinity chromatography, and investigated in vitro effects of chemotherapeutic agents, 5 - FU and Tamoxifen, on the activity of this enzyme for the first time. Results: it was determined that Tamoxifen and 5-FU inhibited cellular viability and 5-FU increased intracellular levels of ROS, whereas Tamoxifen reduced intracellular levels of ROS. In addition, human erythrocyte GST enzyme with 16.2 EU/mg specific activity was purified 265.97-fold with a yield of 35% using ammonium sulfate precipitation and glutathione agarose affinity chromatography. The purity of the enzyme was checked by the SDS-PAGE method. In vitro effects of chemotherapeutics, 5-FU and Tamoxifen, on GST activity purified from human erythrocytes were investigated. The results showed that 5-FU increased the activity of GST in the concentration range of 77 to 1155 μM and that Tamoxifen increased the activity of GST in the concentration range of 0.54 to 2.70 μM. Conclusion: In this study, the effects of tamoxifen and 5-FU chemotherapeutic agents on both MCF-7 cell line and human GST enzyme were examined together for the first time. Our study showed that chemotherapeutic agents (5-FU and Tamoxifen) inhibited cellular viability and Tamoxifen reduced intracellular levels of ROS whereas 5-FU increased intracellular levels of ROS. In addition, 5-FU and Tamoxifen were found to increase the activity of GST enzyme purified from the human erythrocyte.

In vitro Cytotoxic Activity of Salsola oppositifolia Desf. (Amaranthaceae) in a Panel of Tumour Cell Lines

2008 ◽  
Vol 63 (5-6) ◽  
pp. 347-354 ◽  
Author(s):  
Rosa Tundis ◽  
Monica R. Loizzo ◽  
Marco Bonesi ◽  
Federica Menichini ◽  
Giancarlo A. Statti ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Amelanotic Melanoma ◽  
Strong Activity ◽  
Etoac Fraction ◽  
Tumour Cell Lines ◽  
First Time ◽  
Mcf 7

The aim of the present study was to evaluate for the first time the in vitro cytotoxic activity of fractions and isolated flavonols from Salsola oppositifolia Desf. (Amaranthaceae). The nhexane fraction demonstrated an effective cytotoxic activity on the large lung carcinoma and amelanotic melanoma cell lines with IC50 values of 19.1 μg/ml and 24.4 μg/ml, respectively. Also the dichloromethane fraction exhibited cytotoxic activity against COR-L23 (IC50 30.4 μg/ml) and C32 (IC50 33.2 μg/ml) cells, while the EtOAc fraction demonstrated a selective cytotoxic activity against MCF-7 cells (IC50 67.9 μg/ml). The major active constituents of this fraction were isorhamnetin-3-O-glucoside (1) and isorhamnetin-3-O-rutinoside (2), which showed an interesting activity against the cell line MCF-7 with IC50 values of 18.2 and 25.2 μg/ml, respectively. Compound 2 exhibited a strong activity against the hormonedependent prostate carcinoma LNCaP cell line with an IC50 of 20.5 μg/ml. Constituents of S. oppositifolia were identified by GC-MS and NMR analyses.

Identification of benzisoquinolinone derivatives with cytotoxicities from the leaves of Portulaca oleracea

2019 ◽  
Vol 74 (5-6) ◽  
pp. 139-144
Author(s):  
Rong-Rui Wei ◽  
Qin-Ge Ma ◽  
Guo-Yue Zhong ◽  
Ming Yang ◽  
Zhi-Pei Sang
Keyword(s):  
Mass Spectrometry ◽  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
A549 Cell ◽  
Positive Control ◽  
Portulaca Oleracea ◽  
Spectroscopic Methods ◽  
First Time ◽  
Mcf 7

Abstract Three new benzisoquinolinones (1–3), together with seven known benzisoquinolinone derivatives (4–10), were isolated from Portulaca oleracea for the first time. The structures of the isolated compounds (1–10) had been elucidated on the basis of extensive spectroscopic methods including ultraviolet, infrared, mass spectrometry, and nuclear magnetic resonance techniques and by comparison with data reported in the references. All isolated compounds were assayed for cytotoxicities against selected human lines in vitro by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Compounds 1, 2, 4, and 7 showed important cytotoxicities against HCT116, MCF-7, U87, and A549 cell lines with IC50 values in the range of 11.62–84.45 μM, which compared with positive control doxorubicin.

scholarly journals Mitotic arrest affects clustering of tumor cells

Cell Division ◽  
2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Julia Bonnet ◽  
Lise Rigal ◽  
Odile Mondesert ◽  
Renaud Morin ◽  
Gaëlle Corsaut ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Cell Aggregation ◽  
Metastatic Potential ◽  
Mitotic Arrest ◽  
Vitro Assay ◽  
The Impact ◽  
Mcf 7

Abstract Background Cancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate CTC number or the size of CTC clusters. Results In this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we observed that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly and formed loose clusters. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact. Conclusions Altogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells.

scholarly journals Polydopamine-Based “Four-in-One” Versatile Nanoplatforms for Targeted Dual Chemo and Photothermal Synergistic Cancer Therapy

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 507 ◽  
Author(s):  
Liu ◽  
Gao ◽  
Zhou ◽  
Nie ◽  
Cheng ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Anticancer Drug ◽  
Near Infrared ◽  
Polymeric Nanoparticles ◽  
Carcinoma Cells ◽  
Promising Strategy ◽  
Human Breast Carcinoma Cells ◽  
Mcf 7

Abstract: The development of versatile nanoscale drug delivery systems that integrate with multiple therapeutic agents or methods and improve the efficacy of cancer therapy is urgently required. To satisfy this demand, polydopamine (PDA)-modified polymeric nanoplatforms were constructed for the dual loading of chemotherapeutic drugs. The hydrophobic anticancer drug docetaxel (DTX) was loaded into the polymeric nanoparticles (NPs) which were fabricated from the star-shaped copolymer CA-PLGA. Then DTX-loaded NPs were coated with PDA, followed by conjugation of polyelethyl glycol (PEG)-modified targeting ligand aptamer AS1411(Apt) and adsorption of the hydrophilic anticancer drug doxorubicin (DOX). This “four-in-one” nanoplatform, referred to as DTX/NPs@PDA/DOX-PEG-Apt, demonstrated high near-infrared photothermal conversion efficiency and exhibited pH and thermo-responsive drug release behavior. Furthermore, it was able to specifically target MCF-7 human breast carcinoma cells and provide synergistic chemo-photothermal therapy to further improve the anticancer effect both in vitro and in vivo, providing a novel promising strategy for cancer therapy.

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