Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
Add more filters










Database
Language
Publication year range
1.
Int J Radiat Biol ; 98(9): 1484-1494, 2022.
Article in English | MEDLINE | ID: mdl-35020574

ABSTRACT

PURPOSE: Radiation therapy for cancer is limited by damage to surrounding normal tissues, and failure to completely eradicate a tumor. This study investigated a novel radiosensitizer, composed of lutetium phosphate nanoparticles doped with 1% praseodymium and 1.5% neodymium cations (LuPO4:Pr3+,Nd3+). During X-ray exposure, the particles emit UVC photons (200-280 nm), resulting in increased tumor cell death, by oxygen-independent UVC-induced damage. METHODS AND MATERIALS: Specially designed LuPO4:Pr3+,Nd3+ nanoscintillator particles were characterized by dynamic light scattering, TEM and emission spectroscopy upon excitation. Cell death was determined by reduction in tumor spheroid growth over a 3-week period using a 3 D A549 lung cancer model. Cell cycle was evaluated by flow cytometry and cell death pathways were assessed by Annexin V/PI stain as well as quantify apoptotic bodies. RESULTS: Lung cancer cells expressed no long-term or nonspecific toxicity when incubated with LuPO4:Pr3+,Nd3+ nanoscintillators. In contrast, there was significant growth inhibition of cell spheres treated with 2.5 mg/ml LuPO4:Pr3+,Nd3+ in combination with ionizing radiation (4 or 8 Gy X-ray), compared to radiation alone. Homogeneous distribution of small NPs throughout the entire sphere resulted in more pronounced lethality and growth inhibition, compared to particle distribution limited to the outer cell layers. Growth inhibition after the combined treatment was caused by necrosis, apoptosis and G2/M cell cycle arrest. CONCLUSIONS: Newly designed UVC-emitting nanoscintillators (LuPO4:Pr3+,Nd3+) in combination with ionizing radiation cause tumorsphere growth inhibition by inducing cell cycle arrest, apoptosis and necrosis. UVC-emitting nanoparticles offer a promising new strategy for enhancing local tumor response to ionizing radiation treatment.


Subject(s)
Lung Neoplasms , Nanoparticles , Apoptosis/radiation effects , Cell Line, Tumor , Humans , Lung Neoplasms/radiotherapy , Necrosis , Radiation, Ionizing
2.
Semin Cell Dev Biol ; 87: 22-29, 2019 03.
Article in English | MEDLINE | ID: mdl-29727726

ABSTRACT

In planarians, pluripotency can be studied in vivo in the adult animal, making these animals a unique model system where pluripotency-based regeneration (PBR)-and its therapeutic potential-can be investigated. This review focuses on recent findings to build a cloud model of fate restriction likelihood for planarian stem and progenitor cells. Recently, a computational approach based on functional and molecular profiling at the single cell level was proposed for human hematopoietic stem cells. Based on data generated both in vivo and ex vivo, we hypothesized that planarian stem cells could acquire multiple direction lineage biases, following a "badlands" landscape. Instead of a discrete tree-like hierarchy, where the potency of stem/progenitor cells reduces stepwise, we propose a Continuum of LOw-primed UnDifferentiated Planarian Stem/Progenitor Cells (CLOUD-PSPCs). Every subclass of neoblast/progenitor cells is a cloud of likelihood, as the single cell transcriptomics data indicate. The CLOUD-HSPCs concept was substantiated by in vitro data from cell culture; therefore, to confirm the CLOUD-PSPCs model, the planarian community needs to develop new tools, like live cell tracking. Future studies will allow a deeper understanding of PBR in planarian, and the possible implications for regenerative therapies in human.


Subject(s)
Models, Biological , Planarians , Animals , Cell Lineage , Humans
3.
Stem Cell Res ; 32: 65-72, 2018 10.
Article in English | MEDLINE | ID: mdl-30218895

ABSTRACT

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are an invaluable tool for both basic and translational cardiovascular research. The potential that these cells hold for therapy, disease modeling and drug discovery is hampered by several bottlenecks that currently limit both the yield and the efficiency of cardiac induction. Here, we present a complete workflow for the production of ready-to-use hiPSC-CMs in a dynamic suspension bioreactor. This includes the efficient and highly reproducible differentiation of hiPSCs into cardiospheres, which display enhanced physiological maturation compared to static 3D induction in hanging drops, and a novel papain-based dissociation method that offers higher yield and viability than the broadly used dissociation reagents TrypLE and Accutase. Molecular and functional analyses of the cardiomyocytes reseeded after dissociation confirmed both the identity and the functionality of the cells, which can be used in downstream applications, either as monolayers or spheroids.


Subject(s)
Cell Differentiation/physiology , Cell Survival/physiology , Induced Pluripotent Stem Cells/cytology , Myocytes, Cardiac/cytology , Cells, Cultured , Flow Cytometry , Humans , Immunohistochemistry
4.
Dis Model Mech ; 11(9)2018 08 16.
Article in English | MEDLINE | ID: mdl-29967069

ABSTRACT

Planarians have been long known for their regenerative ability, which hinges on pluripotency. Recently, however, the planarian model has been successfully established for routine toxicological screens aimed to assess overproliferation, mutagenicity and tumorigenesis. In this study, we focused on planarian tumor suppressor genes (TSGs) and their role during chemically induced carcinogenic stress in Schmidtea mediterranea Combining in silico and proteomic screens with exposure to human carcinogen type 1A agent cadmium (Cd), we showed that many TSGs have a function in stem cells and that, in general, exposure to Cd accelerated the onset and increased the severity of the observed phenotype. This suggested that the interaction between environmental and genetic factors plays an important role in tumor development in S. mediterranea Therefore, we further focused on the synergistic effects of Cd exposure and p53 knockdown (KD) at the cellular and molecular levels. Cd also produced a specific proteomic landscape in homeostatic animals, with 172 proteins differentially expressed, 43 of which were downregulated. Several of these proteins have tumor suppressor function in human and other animals, namely Wilms Tumor 1 Associated Protein (WT1), Heat Shock Protein 90 (HSP90), Glioma Pathogenesis-Related Protein 1 (GLIPR1) and Matrix Metalloproteinase B (Smed-MMPB). Both Glipr1 and MmpB KD produced large outgrowths, epidermal lesions and epidermal blisters. The epidermal blisters that formed as a consequence of Smed-MmpB KD were populated by smedwi1+ cells, many of which were actively proliferating, while large outgrowths contained ectopically differentiated structures, such as photoreceptors, nervous tissue and a small pharynx. In conclusion, Smed-MmpB is a planarian TSG that prevents stem cell proliferation and differentiation outside the proper milieu.


Subject(s)
Carcinogenesis/genetics , Genes, Tumor Suppressor , Planarians/genetics , Animals , Apoptosis/drug effects , Apoptosis/genetics , Cadmium/toxicity , Carcinogenesis/drug effects , Cell Proliferation , Epidermis/pathology , Gene Expression Regulation, Neoplastic/drug effects , Gene Knockdown Techniques , Homeostasis , Oxidative Stress/drug effects , Phenotype , Proteomics , RNA Interference , Stem Cells/metabolism , Tumor Suppressor Protein p53/metabolism
5.
J Biomed Nanotechnol ; 12(2): 329-36, 2016 Feb.
Article in English | MEDLINE | ID: mdl-27305766

ABSTRACT

Cancer stem cells are demonstrated to be a highly malignant cancer with an extremely high migratory ability and conventional therapies have little effect on preventing cancer migration and invasion. In this study, we investigated the inhibitory effect of zinc sulfide (ZnS) nanoparticles towards the migration and invasion of breast cancer stem cells MCF-7-SC. The cytotoxicity studies and the Hoechst staining experiments suggested that there is no obvious toxicity of ZnS has been observed upto a concentration of 400 µg/mL. ZnS nanoparticles significantly inhibited the wound healing in the MCF-7-SC cells. The cell invasion assay and western blot analysis results suggested that ZnS nanoparticles inhibited the metastasis of MCF-7-SCs in dose-dependent manner by suppressing epithelial-mesenchymal transition process. Overall, our experimental analysis suggested that nano ZnS has the ability to inhibit cancer stem cell migration and invasion, which can open up new insights in the cancer therapy.


Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Movement/drug effects , Nanoparticles/chemistry , Neoplastic Stem Cells/pathology , Sulfides/therapeutic use , Zinc Compounds/therapeutic use , Cell Line, Tumor , Cell Shape/drug effects , Female , Humans , Microscopy, Atomic Force , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Spectrum Analysis, Raman , Sulfides/pharmacology , Sulfides/toxicity , X-Ray Diffraction , Zinc Compounds/pharmacology , Zinc Compounds/toxicity
6.
Phytother Res ; 29(12): 1917-25, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26458283

ABSTRACT

Camphor ((1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one), a bicyclic monoterpene, is one of the major constituents of essential oils from various herbs such as rosemary, lavender, and sage. In this study, we investigated the beneficial effects of camphor as a botanical ingredient in cosmetics. Camphor induced the proliferation of human primary dermal fibroblasts in a dose-dependent manner via the PI3K/AKT and ERK signaling pathways. Camphor attenuated the elevation of senescence associated with ß-galactosidase (SA-ß-gal) activity. Elastase activity decreased, while the total amount of collagen increased, in a dose- and time-dependent manner in human primary dermal fibroblasts treated with camphor. Camphor induced the expression of collagen IA, collagen IIIA, collagen IVA, and elastin in human primary dermal fibroblasts. In addition, posttreatment with 26 and 52 mM camphor for 2 weeks led to a significant reduction in the expression of MMP1 but increases in the expression of collagen IA, IIIA, and elastin in mouse skin exposed to UV for 4 weeks. These posttreatments also reduced the depths of the epidermis and subcutaneous fat layer in UV-exposed mouse skin. Taken together, these findings suggest camphor to be a potent wound healing and antiwrinkle agent with considerable potential for use in cosmeceuticals.


Subject(s)
Camphor/pharmacology , Cellular Senescence/drug effects , Fibroblasts/drug effects , Skin Aging/drug effects , Animals , Cell Proliferation/drug effects , Cells, Cultured , Child , Collagen/metabolism , Elastin/metabolism , Humans , Male , Matricaria/chemistry , Matrix Metalloproteinase 13/metabolism , Mice , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Skin/drug effects , Skin/radiation effects , Skin Aging/radiation effects , Ultraviolet Rays/adverse effects , beta-Galactosidase/metabolism
7.
Chem Biol Drug Des ; 86(4): 496-508, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25582302

ABSTRACT

As some breast cancer-related deaths can be attributed to the metastasis of cancer stem cells, chemotherapeutic agents targeting breast cancer stem cells are of interest as a potential treatment. Flavonoids that exhibit cytotoxicity on breast cancer stem cells have rarely been observed. Thus, the objective of this study was to measure potential cytotoxic effects of 42 different flavonoids on the human breast cancer stem-like cell line, MCF7-SC. The relationship between flavonoid structural properties and cytotoxicity has not been reported previously; therefore, we determined quantitative structure-activity relationships using both comparative molecular field analysis and comparative molecular similarity analysis. Further biological experiments including Western blot analysis, flow cytometry, and immunofluorescence microscopy were also conducted on the most cytotoxic 8-chloroflavanone.


Subject(s)
Antineoplastic Agents , Breast Neoplasms/drug therapy , Cytotoxins , Flavonoids , Neoplastic Stem Cells , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cytotoxins/chemistry , Cytotoxins/pharmacology , Drug Screening Assays, Antitumor , Female , Flavonoids/chemistry , Flavonoids/pharmacology , Humans , MCF-7 Cells
8.
Arch Biochem Biophys ; 562: 92-102, 2014 Nov 15.
Article in English | MEDLINE | ID: mdl-25132643

ABSTRACT

Accumulating evidence has displayed that targeting cancer stem cells (CSCs) is a very promising way for anti-cancer therapies. 2',3'-Dimethoxyflavanone (2',3'-DMF) showed the most potent toxicity of a group of 42 flavonoids tested in MCF-7-SC breast cancer stem cells. 2',3'-DMF triggered intrinsic and extrinsic apoptosis by stimulating the cleavage of PARP and the activation of caspase-9, -8, and -3. Interestingly, 2',3'-DMF induces a dramatic increase in the conversion of LC3, a well-known marker for autophagy. However, acidic vesicular organelles (AVOs), one of the autophagic flux markers were not detected. Co-treatment with chloroquine, the lysosomal inhibitor that blocks autophagic degradation did not show any change in the degree of LC3 conversion, implying that LC3 could play a role in the non-autophagic cell death of MCF-7-SC. We found that 2',3'-DMF induces the ubiquitination of caspase-8, this resulted in an interaction between caspase-8 and LC3, which led to the aggregation and activation of caspase-8. Co-treating cells with 2',3'-DMF and 3-methyladenine, an inhibitor of LC3 lipidation, reduced the activation of caspase-8. These findings provide novel insights into the anti-cancer effects of 2',3'-DMF in breast cancer stem cells by revealing that it induced apoptosis in accompany with the activation of caspase-8 mediated by LC3 conversion.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis , Caspase 8/metabolism , Flavanones/pharmacology , Microtubule-Associated Proteins/metabolism , Neoplastic Stem Cells/cytology , Autophagy , Breast Neoplasms/metabolism , Cell Adhesion , DNA Damage , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Flavones/chemistry , Gene Expression Regulation, Neoplastic , Humans , MCF-7 Cells , Ubiquitin/chemistry , Ubiquitination
SELECTION OF CITATIONS
SEARCH DETAIL
...