scholarly journals Fucoidan Inhibition of Osteosarcoma Cells is Species and Molecular Weight Dependent

Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 104 ◽  
Author(s):  
Dhanak Gupta ◽  
Melissa Silva ◽  
Karolina Radziun ◽  
Diana C. Martinez ◽  
Christopher J. Hill ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cell Death ◽  
Adhesion Formation ◽  
Annexin V ◽  
G1 Phase ◽  
Osteosarcoma Cells ◽  
Anti Cancer ◽  
Induced Apoptosis ◽  
Molecular Weight Fractions ◽  
Crude Fucoidan

Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anti-cancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10–50 kDa), medium (MMW, 50–100 kDa) and high (HMW, >100 kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had the highest levels of sugars, acids and sulphation among molecular weight fractions. There was a dose-dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in the sub-G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress-induced apoptosis-like cell death for F. vesiculosus fucoidan and features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.

scholarly journals Fucoidan Inhibition of Osteosarcoma Cells is Species and Molecular Weight Dependent

2019 ◽  
Author(s):  
Dhanak Gupta ◽  
Melissa Silva ◽  
Karolina Radziun ◽  
Diana Martinez ◽  
Christopher Hill ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cell Death ◽  
Adhesion Formation ◽  
Annexin V ◽  
G1 Phase ◽  
Osteosarcoma Cells ◽  
Anticancer Activities ◽  
Induced Apoptosis ◽  
Molecular Weight Fractions ◽  
Crude Fucoidan

Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anticancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10-50kDa), medium (MMW, 50-100kDa) and high (HMW, >100kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had highest the levels of sugars, acids and sulphation among molecular weight fractions. There was a dose dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in sub G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress induced apoptosis-like cell death for F. vesiculosus fucoidan but features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.

Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death

2019 ◽  
Vol 18 (10) ◽  
pp. 1448-1456 ◽  
Author(s):  
Bahareh Movafegh ◽  
Razieh Jalal ◽  
Zobeideh Mohammadi ◽  
Seyyede A. Aldaghi
Keyword(s):  
Cell Death ◽  
Cellular Uptake ◽  
Combined Treatment ◽  
Annexin V ◽  
Cell Penetrating Peptides ◽  
Short Exposure ◽  
Dependent Manner ◽  
Du145 Cells ◽  
Induced Apoptosis ◽  
Resistance To Doxorubicin

Objective: Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell-penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. Methods: The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and ethidium bromide- acridine orange stainings, flow cytometry using annexin V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3 activity were used to examine the influence of poly-L-arginine on doxorubicininduced cell death. Results: Poly-L-arginine had no cytotoxicity at low concentrations and short exposure times. Poly-L-arginine increased the cytotoxic effect of doxorubicin in DU145 cells in a time-dependent manner. But no significant reduction was found in HFF cell viability. Poly-L-arginine seems to facilitate doxorubicin uptake and increase its intracellular concentration. 24h combined treatment of cells with doxorubicin (0.5 µM) and poly-L-arginine (1 µg ml-1) caused a small increase in doxorubicin-induced apoptosis and significantly elevated necrosis in DU145 cells as compared to each agent alone. Conclusion: Our results indicate that poly-L-arginine at lowest and highest concentrations act as proliferationinducing and antiproliferative agents, respectively. Between these concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and its cytotoxicity through induction of necrosis.

scholarly journals Targeting the hallmarks of cancer: the effects of silibinin on proliferation, cell death, angiogenesis, and migration in colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Saba Sameri ◽  
Chiman Mohammadi ◽  
Mehrnaz Mehrabani ◽  
Rezvan Najafi
Keyword(s):  
Annexin V ◽  
Anticancer Activities ◽  
Scratch Assay ◽  
Anti Cancer ◽  
Different Types ◽  
Colon Cell ◽  
Colon Cell Line ◽  
And Migration ◽  
Induced Apoptosis ◽  
Colony Forming Assay

Abstract Background Silibinin, as a chemopreventive agent, has shown anti-cancer efficacy against different types of cancers. In the present study, we investigated the anti-cancer activities of silibinin on CT26 mouse colon cell line. Methods CT26 cells were treated with different concentrations of silibinin. To examine the cytotoxic effect of silibinin on proliferation, apoptosis, autophagy, angiogenesis, and migration, MTT, colony-forming assay, Annexin V/PI flow cytometry, RT-qPCR, and Scratch assay were used. Results Silibinin was found to significantly reduce CT26 cells survival. Furthermore, silibinin strongly induced apoptosis and autophagy by up-regulating the expression of Bax, Caspase-3, Atg5, Atg7 and BECN1 and down-regulating Bcl-2. Silibinin considerably down-regulated the expression of COX-2, HIF-1α, VEGF, Ang-2, and Ang-4 as well as the expression of MMP-2, MMP-9, CCR-2 and CXCR-4. Conclusions The present study revealed that silibinin shows anticancer activities by targeting proliferation, cell survival, angiogenesis, and migration of CT26 cells.

scholarly journals Induction of cell death in prostate cancer cells by escopoletin, a promising treatment strategy

2015 ◽  
Vol 10 (3) ◽  
pp. 500 ◽  
Author(s):  
Da Chen ◽  
Xiao-Yi Zhang ◽  
Fa-Zhu Zheng ◽  
Hai-Tao Wang ◽  
Jian-Liang Cai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Antioxidant Activities ◽  
Apoptotic Cell ◽  
Annexin V ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Enhanced Expression ◽  
Promising Treatment ◽  
Du145 Cells

<p>Escopoletin, a phenolic compound belonging to anthocyanin family shows promising antioxidant activities. In the present study, anti-cancer effects of escopoletin treatment in DU145 cells were investigated. The sulphorhodamine-B staining and annexin V and propidium iodide were respectively used for the analysis of cell viability and death. The results revealed a significantly higher cytotoxicity by escopoletin that caused cell death in DU145 cells. Escopoletin treatment in DU145 cells markedly inhibited cell growth through non-apoptotic cell death and induced significant reactive oxygen species (ROS) production. It also induced G1 cell cycle arrest and cyclin D1 accumulation through the enhanced expression of p21. However, the effect of escopoletin on DU145 cells was reversed by pretreatment with glutathione antioxidant. This suggests that escopoletin induced generation of ROS is responsible for the increased cytotoxicity in DU145 cells. Thus, escopoletin exhibits potential therapeutic efficacy for the treatment of prostate cancer.</p><p> </p>

scholarly journals β Lapachone blocks the cell cycle and induces apoptosis in canine osteosarcoma cells

2018 ◽  
Vol 38 (12) ◽  
pp. 2224-2232
Author(s):  
Vanessa S. Cruz ◽  
Fernanda A. Rodrigues ◽  
Karla M.S. Braga ◽  
Patrícia A. Machado ◽  
Cesario Bianchi Filho ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Bone Cells ◽  
Annexin V ◽  
Chemotherapeutic Agents ◽  
G1 Phase ◽  
Blue Dye ◽  
Osteosarcoma Cells ◽  
Survival Fraction ◽  
Canine Osteosarcoma

ABSTRACT: Osteosarcoma is a malignant tumor of primitive bone cells with a high incidence in dogs and humans. The need for more effective drugs with less adverse consequences has pushed the development of chemotherapeutic agents from plants and other natural sources. The aim of this study was to verify the cytotoxic effects of β-lapachone, a compound present in the sawdust of Tabebuia sp. (popularly known as ipê) wood, on canine osteosarcoma cells subcultured and treated in different concentrations (0.1μm, 0.3μm e 1.0μm) and exposure times (24h, 48h e 72h). Results were obtained through Trypan blue dye exclusion, tetrazolium reducing method, cell survival assay, Annexin V-FITC and Propidium Iodine labeling, JC-1 dye labeling and cell cycle kinetics e analysis. The group treated with 0.3μm β-lapachone presented higher decrease in cell viability (80.27%, 24h, 47.41%, 48h and 35.19%, 72h) and greater progression of cytotoxicity (19.73%, 24h, 52.59%, 48h and 64.81%, 72h). The lower IC50 (0.180μm) was verified in the group treated for 72 hours. Cell growth after treatment decreased as concentration and time of exposure increased, with 0.50% survival fraction at the concentration of 1.0μm. Initial apoptosis was the most frequent type of cell death in all groups, reaching bottom in the 24-hour group treated with 0.1μm (4.26%) and peaking in the 72-hour group treated with 1.0μm (85.89%). Mitochondrial depolarization demonstrated a dose-dependent phenomenon, indicating the intrinsic apoptosis. Cell growth inhibition by blocking cell cycle in the G0/G1 phase related to the exposure the time. β-lapachone is cytotoxic for canine osteosarcoma cells, induces apoptosis and promotes cell cycle arrest in G0/G1 phase.

scholarly journals The Comprehensive Roles of ATRANORIN, A Secondary Metabolite from the Antarctic Lichen Stereocaulon caespitosum, in HCC Tumorigenesis

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1414 ◽  
Author(s):  
Young-Jun Jeon ◽  
Sanghee Kim ◽  
Ji Hee Kim ◽  
Ui Joung Youn ◽  
Sung-Suk Suh
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Genetic Diseases ◽  
Annexin V ◽  
Cancer Therapeutics ◽  
Metastatic Potential ◽  
Anti Cancer ◽  
Experimental Approaches ◽  
The Antarctic ◽  
Death Determination

Hepatocellular carcinoma (HCC) is one of the most deadly genetic diseases, but surprisingly chemotherapeutic approaches against HCC are only limited to a few targets. In particular, considering the difficulty of a chemotherapeutic drug development in terms of cost and time enforces searching for surrogates to minimize effort and maximize efficiency in anti-cancer therapy. In spite of the report that approximately one thousand lichen-derived metabolites have been isolated, the knowledge about their functions and consequences in cancer development is relatively limited. Moreover, one of the major second metabolites from lichens, Atranorin has never been studied in HCC. Regarding this, we comprehensively analyze the effect of Atranorin by employing representative HCC cell lines and experimental approaches. Cell proliferation and cell cycle analysis using the compound consistently show the inhibitory effects of Atranorin. Moreover, cell death determination using Annexin-V and (Propidium Iodide) PI staining suggests that it induces cell death through necrosis. Lastly, the metastatic potential of HCC cell lines is significantly inhibited by the drug. Taken these together, we claim a novel functional finding that Atranorin comprehensively suppresses HCC tumorigenesis and metastatic potential, which could provide an important basis for anti-cancer therapeutics.

scholarly journals A Novel High-Throughput Technique for Identifying Monoclonal Antibodies capable of Death Receptor Induced Apoptosis

2009 ◽  
Vol 2 ◽  
pp. JCD.S3660
Author(s):  
Hang Fai Kwok ◽  
Julie A. Gormley ◽  
Christopher J. Scott ◽  
James A. Johnston ◽  
Shane A. Olwill
Keyword(s):  
Cell Death ◽  
High Throughput ◽  
High Throughput Screening ◽  
False Negative ◽  
Death Receptor ◽  
Annexin V ◽  
Fas Receptor ◽  
Induced Apoptosis

The study of death receptor family induced apoptosis has gained momentum in recent years with the knowledge that therapeutic antibodies targeting DR4 and DR5 (death receptor's 4 and 5) have proved efficacious in multiple clinical trials. The therapeutic rationale is based on targeting and amplifying a tumour tissues normal cell death programme (apoptosis). While advances in the targeting of DR4 and DR5 have been successful the search for an agonistic antibody to another family member, the Fas receptor, has proven more elusive. This is partly due to the differing in vitro and in vivo characteristics of individual antibodies. In order to induce Fas targeted cell death an antibody must be capable of binding to and trimerising the receptor. It has been shown that antibodies capable of performing this function in vivo, with the assistance of tumour associated cells, do not always induce apoptosis in vitro. As a result the use of current methodologies to detect functional antibodies in vitro may have dismissed potential therapeutic candidates ('false negative'). Here we report a novel high throughput screening technique which artificially cross-links antibodies bound to the Fas receptor. By combining this process with Annexin-V and Prodidium Iodide (PI) staining we can select for antibodies which have the potential to induce apoptosis in vivo.

An Edible, High Molecular Weight Glycoprotein Fraction from Ganoderma Lucidum Inhibits the Akt Pathway in Resistant Myeloma Cell Lines Decreasing Mcl-1 Expression, Up-Regulating FKHR and Inducing Apoptosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4895-4895
Author(s):  
Nazneen Sultana ◽  
Larissa Verda ◽  
Richard K. Burt ◽  
Ann E. Traynor
Keyword(s):  
Molecular Weight ◽  
Ganoderma Lucidum ◽  
Active Material ◽  
Nutritional Supplement ◽  
Myeloma Cell ◽  
Akt Pathway ◽  
Remission Induction ◽  
Scid Mouse Model ◽  
Induced Apoptosis ◽  
Molecular Weight Fractions

Abstract We observed apparent synergy between dexamethsone and a nutritional supplement taken by a patient with poor prognosis plasma cell leukima. The rapidity of the clinical remission induction and the duration of remission, which was sustained without consolidation, suggested possible inhibition of the Akt pathway. A review of the supplements ingested indicated two mycelial derivatives, one of which was Ganoderma Lucidum, (Ling-Zhi, Reishi) a traditional Chinese medicine used to prevent kidney and liver disease and to promote anti-tumor immunity. We obtained a known quantity of certified shell broken spore of G Lucidum from China. Dissolved in 70 degree C water and then diluted as a 2.5% v/v solution in RPMI1640, it induced apoptosis of 80% of OPM6 cells by 72 hours, which was only marginally improved by the addition of1uM dexamethasone. It induced 70% cell death in MM.R cells by 72 hours. This was associated with a 90% reduction in measurable Mcl-1 by Western blot after two hours of incubation. In additon phosphorylation of FKHR was reduced 70% at 2 hours and was undetectable after 72 hours. Phosphorylation of Akt at threonine 308 was reduced 75%. To further purify this activity we separated out molecular weight fractions by Centricon centrifugation. We were able to 10 fold concentrate the active material in the &gt;100,000 MW fraction by centrifugation. Used in the same relative dilution of 2.5% v/v, this concentrate killed between 90% and 96% of glucocorticoid resistant cells at 72 houyrs. Of interest the concentrate induced a lesser degree of apoptosis in corticosteroid sensitive cells, but enhanced the activity of dexamethasone. Spectrophotometry followed by oxidation with sodium meta-periodate and measurement absorption at 550 nm suggested a glycoprotein enrichment in this concentration. Further isolation of the active component of this fraction is underway in order to determine if it is the Lin-Zhi 8 protein sequenced in 1991 or a distinct glycoprotein from the Ganoderma Lucidum. It appears to be an orally tolerable inhibitor of the Akt pathway. It also shows activty in rheumatoid arthritis synovium RAS cells and may have usefulness in T cell supression and graft tolerance.Pre-clinical testing in a SCID mouse model has been begun.

scholarly journals Interactions of hemoglobin with hydrogen peroxide alters thiol levels and course of endothelial cell death

2000 ◽  
Vol 279 (4) ◽  
pp. H1880-H1889 ◽  
Author(s):  
Felice D'Agnillo ◽  
Abdu I. Alayash
Keyword(s):  
Hydrogen Peroxide ◽  
Cell Death ◽  
Endothelial Cell ◽  
Annexin V ◽  
Protective Mechanisms ◽  
Aortic Endothelial Cells ◽  
Deferoxamine Mesylate ◽  
Endothelial Cell Death ◽  
Extensive Degradation ◽  
Induced Apoptosis

We investigated cellular injury and death induced by ultrapure human Hb (HbA0) and its diaspirin cross-linked derivative DBBF-Hb in normal and glutathione (GSH)-depleted bovine aortic endothelial cells subjected to hydrogen peroxide (H2O2). HbA0underwent extensive degradation and heme loss, whereas DBBF-Hb persisted longer in its ferryl (Fe4+) form. The formation of ferryl HbA0 or ferryl DBBF-Hb was associated with a significant decrease in endothelial cell GSH compared with the addition of H2O2 or Hbs alone. This effect was inhibited by catalase, but not by superoxide dismutase or deferoxamine mesylate. The presence of HbA0 and DBBF-Hb reduced H2O2-induced apoptosis, as measured by cell morphology, annexin V binding assay, and caspase inhibition, consistent with the ability to consume H2O2 in an enzyme-like fashion. However, the pattern of cell death and injury produced by HbA0 and DBBF-Hb appeared to be distinctly different among proteins as well as among cells with and without GSH. These findings may have important implications for the use of cell-free Hb as oxygen therapeutics in patients with coexisting pathologies who may lack antioxidant protective mechanisms.

scholarly journals Flow cytometry evaluation of HeLa S3 cell death induced by gamma-radiation

2004 ◽  
Vol 23 (2) ◽  
pp. 135-142 ◽  
Author(s):  
Ana Niciforovic ◽  
Bozidarka Zaric ◽  
Aleksandra Dakic ◽  
Nevena Tisma ◽  
Marija Radojcic
Keyword(s):  
Flow Cytometry ◽  
Cell Death ◽  
Radiation Dose ◽  
Gamma Radiation ◽  
Fluorescent Microscopy ◽  
Annexin V ◽  
Hela S3 ◽  
Induced Apoptosis ◽  
60Co Gamma Radiation

In this study we followed the effects of radiation on human uterin cervix HeLa S3 cells viability, morphology and DNA structure 2-96 hours after treatment with 2-10 Gy from 60Co gamma radiation source. Staining of cells with Annexin V-FITC and propidium iodide showed very low degree of radiation-induced apoptosis. The prevailing form of HeLa S3 cell death according to flow-cytometry, DNA fragmentation and fluorescent microscopy, was necrosis. The gamma-radiation dose necessary to induce 50% of necrosis (termed DD50) was twice higher compared to dose that induced 50% inhibition of cell proliferation (LD50). These in vitro data suggested, that the increase in radiation dose might eradicate tumor cells, rather than just control their proliferation and growth.

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