scholarly journals Perspectives in Manipulating EVs for Therapeutic Applications: Focus on Cancer Treatment

2020 ◽  
Vol 21 (13) ◽  
pp. 4623 ◽  
Author(s):  
Katarzyna Nazimek ◽  
Krzysztof Bryniarski
Keyword(s):  
Membrane Lipids ◽  
Current Knowledge ◽  
Parental Cell ◽  
Target Cells ◽  
Adjuvant Activity ◽  
Micro Rnas ◽  
Anti Cancer ◽  
Research Findings

Extracellular vesicles (EVs) receive special attention from oncologists due to their assumed usefulness as prognostic markers, vaccines to induce anti-cancer immune response, and physiological delivery tools. The latter application, which supports the reduction of side effects of treatment, is still fraught with many challenges, including established methods for loading EVs with selected cargo and directing them towards target cells. EVs could be loaded with selected cargo either in vitro using several physicochemical techniques, or in vivo by modification of parental cell, which may have an advantage over in vitro procedures, since some of them significantly influence EVs’ properties. Otherwise, our research findings suggest that EVs could be passively supplemented with micro RNAs (miRNAs) or miRNA antagonists to induce expected biological effect. Furthermore, our observations imply that antigen-specific antibody light chains could coat the surface of EVs to increase the specificity of cell targeting. Finally, the route of EVs’ administration also determines their bioavailability and eventually induced therapeutic effect. Besides, EV membrane lipids may possibly possess immune adjuvant activity. The review summarizes the current knowledge on the possibilities to manipulate EVs to use them as a delivery tool, with the special emphasis on anti-cancer therapy.

scholarly journals The Occurrence and Biological Activity of Tormentic Acid—A Review

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3797
Author(s):  
Marta Olech ◽  
Wojciech Ziemichód ◽  
Natalia Nowacka-Jechalke
Keyword(s):  
Biological Activity ◽  
Plant Species ◽  
Current Knowledge ◽  
In Vivo Studies ◽  
Natural Sources ◽  
Anti Cancer ◽  
Biochemical Mechanisms ◽  
Tormentic Acid

This review focuses on the natural sources and pharmacological activity of tormentic acid (TA; 2α,3β,19α-trihydroxyurs-2-en-28-oic acid). The current knowledge of its occurrence in various plant species and families is summarized. Biological activity (e.g., anti-inflammatory, antidiabetic, antihyperlipidemic, hepatoprotective, cardioprotective, neuroprotective, anti-cancer, anti-osteoarthritic, antinociceptive, antioxidative, anti-melanogenic, cytotoxic, antimicrobial, and antiparasitic) confirmed in in vitro and in vivo studies is compiled and described. Biochemical mechanisms affected by TA are indicated. Moreover, issues related to the biotechnological methods of production, effective eluents, and TA derivatives are presented.

scholarly journals Anti-Cancer Effects of Green Tea Polyphenols Against Prostate Cancer

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 193 ◽  
Author(s):  
Yasuyoshi Miyata ◽  
Yohei Shida ◽  
Tomoaki Hakariya ◽  
Hideki Sakai
Keyword(s):  
Prostate Cancer ◽  
Green Tea ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Tea Polyphenols ◽  
Green Tea Polyphenols ◽  
Anti Cancer ◽  
Prevention And Treatment

Prostate cancer is the most common cancer among men. Green tea consumption is reported to play an important role in the prevention of carcinogenesis in many types of malignancies, including prostate cancer; however, epidemiological studies show conflicting results regarding these anti-cancer effects. In recent years, in addition to prevention, many investigators have shown the efficacy and safety of green tea polyphenols and combination therapies with green tea extracts and anti-cancer agents in in vivo and in vitro studies. Furthermore, numerous studies have revealed the molecular mechanisms of the anti-cancer effects of green tea extracts. We believe that improved understanding of the detailed pathological roles at the molecular level is important to evaluate the prevention and treatment of prostate cancer. Therefore, in this review, we present current knowledge regarding the anti-cancer effects of green tea extracts in the prevention and treatment of prostate cancer, with a particular focus on the molecular mechanisms of action, such as influencing tumor growth, apoptosis, androgen receptor signaling, cell cycle, and various malignant behaviors. Finally, the future direction for the use of green tea extracts as treatment strategies in patients with prostate cancer is introduced.

Reversine: A Synthetic Purine with a Dual Activity as a Cell Dedifferentiating Agent and a Selective Anticancer Drug

2020 ◽  
Vol 27 (21) ◽  
pp. 3448-3462
Author(s):  
Marco Piccoli ◽  
Andrea Ghiroldi ◽  
Michelle M. Monasky ◽  
Federica Cirillo ◽  
Giuseppe Ciconte ◽  
...  
Keyword(s):  
Stem Cells ◽  
Current Knowledge ◽  
Embryonic Stem ◽  
Cell Types ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Adult Cell ◽  
Induced Pluripotent

The development of new therapeutic applications for adult and embryonic stem cells has dominated regenerative medicine and tissue engineering for several decades. However, since 2006, induced Pluripotent Stem Cells (iPSCs) have taken center stage in the field, as they promised to overcome several limitations of the other stem cell types. Nonetheless, other promising approaches for adult cell reprogramming have been attempted over the years, even before the generation of iPSCs. In particular, two years before the discovery of iPSCs, the possibility of synthesizing libraries of large organic compounds, as well as the development of high-throughput screenings to quickly test their biological activity, enabled the identification of a 2,6-disubstituted purine, named reversine, which was shown to be able to reprogram adult cells to a progenitor-like state. Since its discovery, the effect of reversine has been confirmed on different cell types, and several studies on its mechanism of action have revealed its central role in inhibitory activity on several kinases implicated in cell cycle regulation and cytokinesis. These key features, together with its chemical nature, suggested a possible use of the molecule as an anti-cancer drug. Remarkably, reversine exhibited potent cytotoxic activity against several tumor cell lines in vitro and a significant effect in decreasing tumor progression and metastatization in vivo. Thus, 15 years since its discovery, this review aims at critically summarizing the current knowledge to clarify the dual role of reversine as a dedifferentiating agent and anti-cancer drug.

scholarly journals Effect of Mesenchymal Stem Cell-Derived Exosomes on Retinal Injury: A Review of Current Findings

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Raffaele Nuzzi ◽  
Paolo Caselgrandi ◽  
Alessandro Vercelli
Keyword(s):  
Current Knowledge ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Retinal Damage ◽  
Phospholipid Membrane ◽  
Retinal Injury ◽  
Immunological Rejection ◽  
Reduction Effect

In recent years, various studies have followed in the literature on the therapeutic effects of mesenchymal stem cells (MSC) on damage in retinal cells. The evidence that MSCs exert their regenerative and damage reduction effect in a paracrine way, through the release of soluble factors and exosomes, is now consolidated. Exosomes are microvesicles formed by a double layer of phospholipid membrane and carry proteins and RNA, through which they play a therapeutic role on target cells. Scientific research has recently focused on the use of exosomes derived from MSC in various models of retinal damage in vitro and in vivo as they, compared to MSCs, have similar functions and at the same time have different advantages such as greater stability and handling, a lower chance of immunological rejection and no risk of malignant transformation. The purpose of this review is to summarize current knowledge on the therapeutic use of exosomes derived from MSCs in retinal damage and to stimulate new clinical perspectives regarding their use.

scholarly journals The Triad Hsp60-miRNAs-Extracellular Vesicles in Brain Tumors: Assessing Its Components for Understanding Tumorigenesis and Monitoring Patients

2021 ◽  
Vol 11 (6) ◽  
pp. 2867
Author(s):  
Francesca Graziano ◽  
Domenico Gerardo Iacopino ◽  
Giacomo Cammarata ◽  
Gianluca Scalia ◽  
Claudia Campanella ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Disease Status ◽  
Experimental Models ◽  
Host Cells ◽  
Target Cells ◽  
Original Cell

Brain tumors have a poor prognosis and progress must be made for developing efficacious treatments, but for this to occur their biology and interaction with the host must be elucidated beyond current knowledge. What has been learned from other tumors may be applied to study brain tumors, for example, the role of Hsp60, miRNAs, and extracellular vesicles (EVs) in the mechanisms of cell proliferation and dissemination, and resistance to immune attack and anticancer drugs. It has been established that Hsp60 increases in cancer cells, in which it occurs not only in the mitochondria but also in the cytosol and plasma-cell membrane and it is released in EVs into the extracellular space and in circulation. There is evidence suggesting that these EVs interact with cells near and far from their original cell and that this interaction has an impact on the functions of the target cell. It is assumed that this crosstalk between cancer and host cells favors carcinogenesis in various ways. We, therefore, propose to study the triad Hsp60-related miRNAs-EVs in brain tumors and have standardized methods for the purpose. These revealed that EVs with Hsp60 and related miRNAs increase in patients’ blood in a manner that reflects disease status. The means are now available to monitor brain tumor patients by measuring the triad and to dissect its effects on target cells in vitro, and in experimental models in vivo.

scholarly journals Modeling Pharmacokinetic Profiles for Assessment of Anti-Cancer Drug on a Microfluidic System

Micromachines ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 551
Author(s):  
Yaqiong Guo ◽  
Pengwei Deng ◽  
Wenwen Chen ◽  
Zhongyu Li
Keyword(s):  
Drug Administration ◽  
Drug Concentration ◽  
Drug Exposure ◽  
Microfluidic System ◽  
Cancer Drug ◽  
Target Cells ◽  
Anti Cancer ◽  
Pharmaceutical Activity

The pharmacokinetic (PK) properties of drug, which include drug absorption and excretion, play an important role in determining the in vivo pharmaceutical activity. However, current in vitro systems that model PK profiles are often limited by the in vivo-like concentration profile of a drug. Herein, we present a perfused and multi-layered microfluidic chip system to model the PK profile of anti-cancer drug 5-FU in vitro. The chip device contains two layers of culture channels sandwiched by a porous membrane, which allows for drug exposure and diffusion between the two channels. The integration of upper intestine cells (Caco-2) and bottom targeted cells within the device enables the generation of loading and clearance portions of a PK curve under peristaltic flow. Fluorescein as a test molecule was initially used to generate a concentration-time curve, investigating the effects of parameters of flow rate, administration time, and initial concentration on dynamic drug concentration profiles. Furthermore, anti-cancer drug 5-FU was performed to assess its pharmaceutical activity on target cells (human lung adenocarcinoma cells or human pulmonary alveolar epithelial cells) using different drug administration regimens. A dynamic, in vivo-like 5-FU exposure refers to PK profile regimen, led to generate a lower drug concentration (dynamically fluctuate from 0 to 1 μg/mL affected by absorption) compared to the constant exposure. Moreover, the PK profile regimen alleviates the drug-induced cytotoxicity on target cells. These results demonstrate the feasibility of determining the PK profiles using this microfluidic system with in vivo-like drug administration regimens. This established system may provide a powerful platform for the prediction of drug safety and effectiveness in the pharmaceutical research.

scholarly journals The Biological and Biophysical Properties of the Spider Peptide Gomesin

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1733 ◽  
Author(s):  
John Tanner ◽  
Evelyne Deplazes ◽  
Ricardo Mancera
Keyword(s):  
Cytotoxic Activity ◽  
Current Knowledge ◽  
Cytotoxic Activities ◽  
Binding Properties ◽  
Anti Cancer ◽  
Specific Selectivity ◽  
Cell Type Specific ◽  
Molecular Mechanism Of Action

This review summarises the current knowledge of Gomesin (Gm), an 18-residue long, cationic anti-microbial peptide originally isolated from the haemocytes of the Brazilian tarantula Acanthoscurria gomesiana. The peptide shows potent cytotoxic activity against clinically relevant microbes including Gram-positive and Gram-negative bacteria, fungi, and parasites. In addition, Gm shows in-vitro and in-vivo anti-cancer activities against several human and murine cancers. The peptide exerts its cytotoxic activity by permeabilising cell membranes, but the underlying molecular mechanism of action is still unclear. Due to its potential as a therapeutic agent, the structure and membrane-binding properties, as well as the leakage and cytotoxic activities of Gm have been studied using a range of techniques. This review provides a summary of these studies, with a particular focus on biophysical characterisation studies of peptide variants that have attempted to establish a structure-activity relationship. Future studies are still needed to rationalise the binding affinity and cell-type-specific selectivity of Gm and its variants, while more pre-clinical studies are required to develop Gm into a therapeutically useful peptide.

scholarly journals The FomA Porin from Fusobacterium nucleatum Is a Toll-Like Receptor 2 Agonist with Immune Adjuvant Activity

2012 ◽  
Vol 19 (7) ◽  
pp. 1093-1101 ◽  
Author(s):  
Deana N. Toussi ◽  
Xiuping Liu ◽  
Paola Massari
Keyword(s):  
Fusobacterium Nucleatum ◽  
Target Cells ◽  
Toll Like Receptor ◽  
Adjuvant Effect ◽  
Adjuvant Activity ◽  
Content Type ◽  
Enhanced Production ◽  
Immune Adjuvant

ABSTRACTMany bacterial components selectively activate immune and nonhematopoietic target cells via Toll-like receptor (TLR) signaling; modulation of such host responses defines the immune adjuvant properties of these bacterial products. For example, the outer membrane protein porins fromNeisseria,Salmonella, andShigellaare known TLR2 agonists with established systemic and mucosal immune adjuvanticity. Early work indicated that the FomA porin fromFusobacterium nucleatumhas immune adjuvant activity in mice. Using a purified recombinant FomA, we have verified its immune stimulatory properties and have defined a role for TLR2 signaling in itsin vitroandin vivoactivity. FomA induces interleukin 8 (IL-8) secretion and NF-κB-dependent luciferase activity in HEK cells expressing TLR2, IL-6 secretion, and cell surface upregulation of CD86 and major histocompatibility complex (MHC) II in primary B cells from wild-type mice, but it fails to activate cells from TLR2 knockout mice. Accordingly, the immune adjuvant activity of FomA is also TLR2 dependent. In a mouse model of immunization with ovalbumin (OVA), FomA induces enhanced production of OVA-specific IgM and IgG, including IgG1 and IgG2b antibodies, as well as enhanced secretion of IL-10 and IL-6, consistent with a Th2-type adjuvant effect. We also observe a moderate production of anti-FomA antibodies, suggesting that FomA is also immunogenic, a quality that is also TLR2 dependent. Therefore, modulation of host immune responses by FomA may be effective for targeting general host immunity not only to pathogens (as a novel TLR2 adjuvant) but also toF. nucleatumitself (as an antigen), expanding its use as a self-adjuvanted antigen in an immunization strategy against polymicrobial infections, including those byF. nucleatum.

scholarly journals Arthrospira Platensis – Potential in Dermatology and Beyond

2018 ◽  
Vol 6 (1) ◽  
pp. 176-180 ◽  
Author(s):  
Uwe Wollina ◽  
Cristiana Voicu ◽  
Serena Gianfaldoni ◽  
Torello Lotti ◽  
Katlein França ◽  
...  
Keyword(s):  
Arthrospira Platensis ◽  
Current Data ◽  
Resistant Bacteria ◽  
Target Cells ◽  
Non Melanoma Skin Cancer ◽  
Anti Cancer ◽  
Ancient Times ◽  
Melanoma Skin

The search for natural products with benefits for health in general and of potential for treating human disease has gained wider interest world-wide. Here, we analyse current data on the microalga Arthrospira platensis (AP), that has been used in nutrition since ancient times in Fare East and African communities, for medical purposes with a focus on dermatology. Extracts of AP have been investigated in vitro and in vivo. The alga is rich in proteins, lipopolysaccharides and gamma-linolenic acid. AP extracts, phycocyanin compounds and polysaccharide calcium spirulan (Ca-SP) have been evaluated in various models. It could be demonstrated, that AP has significant antioxidant activity, prevents viruses from entry into target cells and inhibits the colonisation of wounds by multi-resistant bacteria. Furthermore, anti-cancer activity was documented in models of oral cancer, melanoma, and UV-induced non-melanoma skin cancer.

scholarly journals An Insight into the Anti-Angiogenic and Anti-Metastatic Effects of Oridonin: Current Knowledge and Future Potential

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 775
Author(s):  
Nurul Akmaryanti Abdullah ◽  
Nur Fariesha Md Hashim ◽  
Aula Ammar ◽  
Noraina Muhamad Zakuan
Keyword(s):  
Cancer Therapy ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Angiogenic Growth Factors ◽  
Mesenchymal Transition ◽  
Anti Cancer

Cancer is one of the leading causes of death worldwide, with a mortality rate of more than 9 million deaths reported in 2018. Conventional anti-cancer therapy can greatly improve survival however treatment resistance is still a major problem especially in metastatic disease. Targeted anti-cancer therapy is increasingly used with conventional therapy to improve patients’ outcomes in advanced and metastatic tumors. However, due to the complexity of cancer biology and metastasis, it is urgent to develop new agents and evaluate the anti-cancer efficacy of available treatments. Many phytochemicals from medicinal plants have been reported to possess anti-cancer properties. One such compound is known as oridonin, a bioactive component of Rabdosia rubescens. Several studies have demonstrated that oridonin inhibits angiogenesis in various types of cancer, including breast, pancreatic, lung, colon and skin cancer. Oridonin’s anti-cancer effects are mediated through the modulation of several signaling pathways which include upregulation of oncogenes and pro-angiogenic growth factors. Furthermore, oridonin also inhibits cell migration, invasion and metastasis via suppressing epithelial-to-mesenchymal transition and blocking downstream signaling targets in the cancer metastasis process. This review summarizes the recent applications of oridonin as an anti-angiogenic and anti-metastatic drug both in vitro and in vivo, and its potential mechanisms of action.

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