scholarly journals Emerging Anticancer Potentials of Selenium on Osteosarcoma

2019 ◽  
Vol 20 (21) ◽  
pp. 5318 ◽  
Author(s):  
Kok-Lun Pang ◽  
Kok-Yong Chin

Selenium is a trace element essential to humans and forms complexes with proteins, which exert physiological functions in the body. In vitro studies suggested that selenium possesses anticancer effects and may be effective against osteosarcoma. This review aims to summarise current evidence on the anticancer activity of inorganic and organic selenium on osteosarcoma. Cellular studies revealed that inorganic and organic selenium shows cytotoxicity, anti-proliferative and pro-apoptotic effects on various osteosarcoma cell lines. These actions may be mediated by oxidative stress induced by selenium compounds, leading to the activation of p53, proapoptotic proteins and caspases. Inorganic selenium is selective towards cancer cells, but can cause non-selective cell death at a high dose. This condition challenges the controlled release of selenium from biomaterials. Selenium treatment in animals inoculated with osteosarcoma reduced the tumour size, but did not eliminate the incidence of osteosarcoma. Only one study investigated the relationship between selenium and osteosarcoma in humans, but the results were inconclusive. In summary, although selenium may exert anticancer properties on osteosarcoma in experimental model systems, its effects in humans require further investigation.

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2019 ◽  
Author(s):  
Joerg Fellenberg ◽  
Burkhard Lehner ◽  
Heiner Saehr ◽  
Astrid Schenker ◽  
Pierre Kunz

Since the introduction of high-dose chemotherapy about 35 years ago, survival rates of osteosarcoma patients have not been significantly improved. New therapeutic strategies replacing or complementing conventional chemotherapy are therefore urgently required. MicroRNAs represent promising targets for such new therapies, as they are involved in the pathology of multiple types of cancer, and aberrant expression of several miRNAs has already been shown in osteosarcoma. In this study, we identified silencing of miR-127-3p and miR-376a-3p in osteosarcoma cell lines and tissues and investigated their role as potential tumor suppressors in vitro and in vivo. Transfection of osteosarcoma cells (n = 6) with miR-127-3p and miR-376a-3p mimics significantly inhibited proliferation and reduced the colony formation capacity of these cells. In contrast, we could not detect any influence of miRNA restoration on cell cycle and apoptosis induction. The effects of candidate miRNA restoration on tumor engraftment and growth in vivo were analyzed using a chicken chorioallantoic membrane (CAM) assay. Cells transfected with mir-127-3p and miR-376a-3p showed reduced tumor take rates and tumor volumes and a significant decrease of the cumulative tumor volumes to 41% and 54% compared to wildtype cells. The observed tumor suppressor function of both analyzed miRNAs indicates these miRNAs as potentially valuable targets for the development of new therapeutic strategies for the treatment of osteosarcoma.


Author(s):  
S.S. Vajpeyee ◽  
J. Ramesh ◽  
R. Karunakaran ◽  
J. Muralidharan ◽  
V. Sankar

Background: Selenium is an important trace mineral required by the animals. It is an integral part of antioxidant system, protecting the body against free radical injury. Nano particles attract a widespread attention due to its high bioavailability and efficacy. The current study was aimed to synthesize, characterize nano selenium and evaluate the cytotoxic effect of nano selenium and organic selenium (selenocysteine) under in vitro condition in vero cell line. Methods: Nano selenium was synthesized by wet chemical method by using sodium selenite, selenium powder, ascorbic acid and sodium hydroxide at laboratory level. In this study particle size, shape, zeta potential and selenium content were characterized by using Particle Size Analyser (PSA), Transmission Electron Microscope (TEM) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The toxicity was analysed by MTT assay against vero cell line. Result: The result revealed that selenium nano particles were spherical in shape, nano in size (less than 50 nm) and pure in nature. The nano selenium and organic selenium (selenocysteine) effectively inhibited the growth of vero cells in a dose dependent manner.


Author(s):  
Nilima Dinesh Kumar ◽  
Bram M. ter Ellen ◽  
Ellen M. Bouma ◽  
Berit Troost ◽  
Denise P. I. van de Pol ◽  
...  

Antiviral therapies are urgently needed to treat and limit the development of severe COVID-19 disease. Ivermectin, a broad-spectrum anti-parasitic agent, has been shown to have anti-SARS-CoV-2 activity in Vero cells at a concentration of 5 μM. These limited in vitro results triggered the investigation of ivermectin as a treatment option to alleviate COVID-19 disease. In April 2021, the World Health Organization stated, however, the following: “the current evidence on the use of ivermectin to treat COVID-19 patients is inconclusive”. It is speculated that the in vivo concentration of ivermectin is too low to exert a strong antiviral effect. Here, we performed a head-to head comparison of the antiviral activity of ivermectin and the structurally related, but metabolically more stable, moxidectin in multiple in vitro models of SARS-CoV-2 infection, including physiologically relevant human respiratory epithelial cells. Both moxidectin and ivermectin exhibited antiviral activity in Vero E6 cells. Subsequent experiments revealed that the compounds predominantly act on a step after virus cell entry. Surprisingly, however, in human airway-derived cell models, moxidectin and ivermectin failed to inhibit SARS-CoV-2 infection, even at a concentration of 10 μM. These disappointing results call for a word of caution in the interpretation of anti-SARS-CoV-2 activity of drugs solely based on Vero cells. Altogether, these findings suggest that, even by using a high-dose regimen of ivermectin or switching to another drug in the same class are unlikely to be useful for treatment against SARS-CoV-2 in humans.


2018 ◽  
Vol 6 (3) ◽  
pp. 114-119 ◽  
Author(s):  
Magdalena Rojewska ◽  
Małgorzata Popis ◽  
Maurycy Jankowski ◽  
Dorota Bukowska ◽  
Paweł Antosik ◽  
...  

AbstractStem cells are cells that have the potential to replicate and/or differentiate, becoming any tissue. This process could be theoretically repeated indefinitely and can be used to create or fix damaged parts any organ. There are many in vivo factors that cause stem cells to replicate and differentiate. Many of these interactions and mechanisms are still unknown. In vitro models have been successful in inducing stem cells to differentiate into the desired lineage using controlled methods. Recently, epithelial tissue has been successfully created using scaffolds on which stem cells are grown in vitro and then transplanted into the host. This transition creates significant problems. This is because in vitro -grown stem cells or stem cell-derived tissues are created in an isolated environment where virtually every aspect can be monitored and controlled. In vivo monitoring and controlling is significantly more difficult for a plethora of reasons. Cells in the body are constantly exposed to many signals and molecules which affect them. Many of the mechanisms behind these interactions and reactions are known but many others are not. As the corpus of knowledge grows, stem cells become closer to being applied in a clinical setting. In this paper, we review the current evidence on stem cell therapy in regenerative medicine and some of the challenges this field faces.


2018 ◽  
Vol 19 (9) ◽  
pp. 2788 ◽  
Author(s):  
Guang Yang ◽  
Hyenjong Hong ◽  
April Torres ◽  
Kristen Malloy ◽  
Gourav Choudhury ◽  
...  

Humans and nonhuman primates (NHP) are similar in behavior and in physiology, specifically the structure, function, and complexity of the immune system. Thus, NHP models are desirable for pathophysiology and pharmacology/toxicology studies. Furthermore, NHP-derived induced pluripotent stem cells (iPSCs) may enable transformative developmental, translational, or evolutionary studies in a field of inquiry currently hampered by the limited availability of research specimens. NHP-iPSCs may address specific questions that can be studied back and forth between in vitro cellular assays and in vivo experimentations, an investigational process that in most cases cannot be performed on humans because of safety and ethical issues. The use of NHP model systems and cell specific in vitro models is evolving with iPSC-based three-dimensional (3D) cell culture systems and organoids, which may offer reliable in vitro models and reduce the number of animals used in experimental research. IPSCs have the potential to give rise to defined cell types of any organ of the body. However, standards for deriving defined and validated NHP iPSCs are missing. Standards for deriving high-quality iPSC cell lines promote rigorous and replicable scientific research and likewise, validated cell lines reduce variability and discrepancies in results between laboratories. We have derived and validated NHP iPSC lines by confirming their pluripotency and propensity to differentiate into all three germ layers (ectoderm, mesoderm, and endoderm) according to standards and measurable limits for a set of marker genes. The iPSC lines were characterized for their potential to generate neural stem cells and to differentiate into dopaminergic neurons. These iPSC lines are available to the scientific community. NHP-iPSCs fulfill a unique niche in comparative genomics to understand gene regulatory principles underlying emergence of human traits, in infectious disease pathogenesis, in vaccine development, and in immunological barriers in regenerative medicine.


2018 ◽  
Vol 2018 ◽  
pp. 1-39 ◽  
Author(s):  
Islam Rady ◽  
Melissa B. Bloch ◽  
Roxane-Cherille N. Chamcheu ◽  
Sergette Banang Mbeumi ◽  
Md Rafi Anwar ◽  
...  

Graviola (Annona muricata) is a small deciduous tropical evergreen fruit tree, belonging to the Annonaceae family, and is widely grown and distributed in tropical and subtropical regions around the world. The aerial parts of graviola have several functions: the fruits have been widely used as food confectionaries, while several preparations, especially decoctions of the bark, fruits, leaves, pericarp, seeds, and roots, have been extensively used in traditional medicine to treat multiple ailments including cancers by local communities in tropical Africa and South America. The reported therapeutic benefits of graviola against various human tumors and disease agents in in vitro culture and preclinical animal model systems are typically tested for their ability to specifically target the disease, while exerting little or no effect on normal cell viability. Over 212 phytochemical ingredients have been reported in graviola extracts prepared from different plant parts. The specific bioactive constituents responsible for the major anticancer, antioxidant, anti-inflammatory, antimicrobial, and other health benefits of graviola include different classes of annonaceous acetogenins (metabolites and products of the polyketide pathway), alkaloids, flavonoids, sterols, and others. This review summarizes the current understanding of the anticancer effects of A. muricata and its constituents on diverse cancer types and disease states, as well as efficacy and safety concerns. It also includes discussion of our current understanding of possible mechanisms of action, with the hope of further stimulating the development of improved and affordable therapies for a variety of ailments.


2017 ◽  
Vol 8 (4) ◽  
pp. 411-417 ◽  
Author(s):  
M.-A. Sirard

Medically assisted reproductive technologies, such as in vitro embryo production, are increasingly being used to palliate infertility. Eggs are produced following a hormonal regimen that stimulates the ovaries to produce a large number of oocytes. Collected oocytes are then fertilized in vitro and allowed to develop in vitro until they are either frozen or transferred to mothers. There are controversial reports on the adverse impacts of these technologies on early embryos and their potential long-term effects. Using newly developed technological platforms that enable global gene expression and global DNA methylation profiling, we evaluated gene perturbations caused by such artificial procedures. We know that cells in the early embryo produce all cells in the body and are able to respond to their in vitro environment. However, it is not known whether gene perturbations are part of a normal response to the environment or are due to distress and will have long-term impacts. While the mouse is an established genetic model used for quality control of culture media in clinics, the bovine is a large mono-ovulating mammal with similar embryonic kinetics as humans during the studied developmental window. These model systems are critical to understand the effects of assisted reproduction without the confounding impact of infertility and without the limitations imposed by the scarcity of donated human samples and ethical issues. The data presented in this review come mostly from our own experimentation, publications, and collaborations. Together they demonstrate that the in vitro environment has a significant impact on embryos at the transcriptomic level and at the DNA methylation level.


2021 ◽  
Author(s):  
Nilima Dinesh Kumar ◽  
Bram Ter Ellen ◽  
Ellen M Bouma ◽  
Berit Troost ◽  
Denise P. I van de Pol ◽  
...  

Antiviral therapies are urgently needed to treat and limit the development of severe COVID-19 disease. Ivermectin, a broad-spectrum anti-parasitic agent, has been shown to have anti-SARS-CoV-2 activity in Vero cells at a concentration of 5 micromolar. These in vitro results triggered the investigation of ivermectin as a treatment option to alleviate COVID-19 disease. In April 2021, the World Health Organization stated, however, the following: "the current evidence on the use of ivermectin to treat COVID-19 patients is inconclusive". It is speculated that the in vivo concentration of ivermectin is too low to exert a strong antiviral effect. Here, we performed a head-to head comparison of the antiviral activity of ivermectin and a structurally related, but metabolically more stable, moxidectin in multiple in vitro models of SARS-CoV-2 infection, including physiologically relevant human respiratory epithelial cells. Both moxidectin and ivermectin exhibited antiviral activity in Vero E6 cells. Subsequent experiments revealed that the compounds predominantly act on a step after virus cell entry. Surprisingly, however, in human airway-derived cell models, moxidectin and ivermectin failed to inhibit SARS-CoV-2 infection, even at a concentration of 10 micromolar. These disappointing results calls for a word of caution in the interpretation of anti-SARS-CoV-2 activity of drugs solely based on Vero cells. Altogether, these findings suggest that, even by using a high-dose regimen of ivermectin or switching to another drug in the same class are unlikely to be useful for treatment against SARS-CoV-2 in humans.


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