scholarly journals Usnic Acid Derivatives as Cytotoxic Agents Against Cancer Cells and the Mechanisms of Their Activity

2019 ◽  
Vol 5 (6) ◽  
pp. 429-439 ◽  
Author(s):  
Beata Guzow-Krzemińska ◽  
Katarzyna Guzow ◽  
Anna Herman-Antosiewicz
Keyword(s):  
Cancer Cells ◽  
Tumour Growth ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Parent Compound ◽  
Usnic Acid ◽  
Xenograft Model ◽  
Mechanisms Of Action ◽  
Cytotoxic Agents ◽  
Lead Compound

Abstract Purpose of Review This article summarises recent research on modifications of the structure or formula of usnic acid (UA), a lichen secondary metabolite, in order to obtain derivatives with higher bioavailability, potency and selectivity against cancer cells and presents the current knowledge on the mechanisms of action of such compounds. Recent Findings Numerous approaches have been undertaken to improve bioactivity of UA concerning its use as an anticancer drug. Among them, the synthesis of UA salts or complexation with 2-hydroxypropyl-β-cyclodextrin to improve its solubility and the encapsulation using different carriers (including various nanomaterials) to stabilise UA in biological fluids and improve their penetrance to, and release in, cancer cells were applied.. Synthetic modification of the UA structure has been explored to obtain more active and cancer-specific derivatives. Recent work indicates that some modifications of the C or A ring of UA selectively increase its antiproliferative potential against cancer cells. Moreover, specific changes in the UA structure allow to obtain derivatives which inhibit enzymes important for the cancer cells’ survival, such as mTOR, Pim, TDP1 or PARP. Some of them have been shown to enhance anticancer activity of the already approved chemotherapeutics, such as topotecan. Others, when used in an animal cancer xenograft model, were superior to UA in retardation of tumour growth and less toxic that the parent compound. Summary UA is a promising lead compound for synthesis of anticancer drugs. Further work on its modifications, mechanisms of activity and validation in animal models is critical for development of effective therapeutics.

scholarly journals Pt(iv) derivatives of cisplatin and oxaliplatin with phenylbutyrate axial ligands are potent cytotoxic agents that act by several mechanisms of action

2016 ◽  
Vol 7 (3) ◽  
pp. 2381-2391 ◽  
Author(s):  
Raji Raveendran ◽  
Jeremy Phillip Braude ◽  
Ezequiel Wexselblatt ◽  
Vojtech Novohradsky ◽  
Olga Stuchlikova ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mechanisms Of Action ◽  
Cytotoxic Agents ◽  
Cytotoxic Agent ◽  
Axial Ligands ◽  
Cellular Pathways ◽  
Derivatives Of

The Pt(iv) derivative of cisplatin,ctc-[Pt(NH3)2(PhB)2Cl2], is a p53 independent very potent cytotoxic agent that kills cancer cells by triggering various cellular pathways.

scholarly journals Embryonic zebrafish xenograft assay of human cancer metastasis

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1682 ◽  
Author(s):  
David Hill ◽  
Lanpeng Chen ◽  
Ewe Snaar-Jagalska ◽  
Bill Chaudhry
Keyword(s):  
Cancer Cells ◽  
Cancer Biology ◽  
Tumour Growth ◽  
Cancer Metastasis ◽  
Human Cancer ◽  
Xenograft Model ◽  
Laboratory Model ◽  
Zebrafish Embryos ◽  
Invasion And Metastasis ◽  
Human Cancer Cells

Cancer metastasis is the most important prognostic factor determining patient survival, but currently there are very few drugs or therapies that specifically inhibit the invasion and metastasis of cancer cells. Currently, human cancer metastasis is largely studied using transgenic and immunocompromised mouse xenograft models, which are useful for analysing end-point tumour growth but are unable to accurately and reliably monitor in vivo invasion, intravasation, extravasation or secondary tumour formation of human cancer cells. Furthermore, limits in our ability to accurately monitor early stages of tumour growth and detect micro-metastases likely results in pain and suffering to the mice used for cancer xenograft experiments. Zebrafish (Danio rerio) embryos, however, offer many advantages as a model system for studying the complex, multi-step processes involved during cancer metastasis. This article describes a detailed method for the analysis of human cancer cell invasion and metastasis in zebrafish embryos before they reach protected status at 5 days post fertilisation. Results demonstrate that human cancer cells actively invade within a zebrafish microenvironment, and form metastatic tumours at secondary tissue sites, suggesting that the mechanisms involved during the different stages of metastasis are conserved between humans and zebrafish, supporting the use of zebrafish embryos as a viable model of human cancer metastasis. We suggest that the embryonic zebrafish xenograft model of human cancer is a tractable laboratory model that can be used to understand cancer biology, and as a direct replacement of mice for the analysis of drugs that target cancer invasion and metastasis.

scholarly journals Embryonic zebrafish xenograft assay of human cancer metastasis

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1682 ◽  
Author(s):  
David Hill ◽  
Lanpeng Chen ◽  
Ewe Snaar-Jagalska ◽  
Bill Chaudhry
Keyword(s):  
Cancer Cells ◽  
Cancer Biology ◽  
Tumour Growth ◽  
Cancer Metastasis ◽  
Human Cancer ◽  
Xenograft Model ◽  
Laboratory Model ◽  
Zebrafish Embryos ◽  
Invasion And Metastasis ◽  
Human Cancer Cells

Cancer metastasis is the most important prognostic factor determining patient survival, but currently there are very few drugs or therapies that specifically inhibit the invasion and metastasis of cancer cells. Currently, human cancer metastasis is largely studied using transgenic and immunocompromised mouse xenograft models, which are useful for analysing end-point tumour growth but are unable to accurately and reliably monitor in vivo invasion, intravasation, extravasation or secondary tumour formation of human cancer cells. Furthermore, limits in our ability to accurately monitor early stages of tumour growth and detect micro-metastases likely results in pain and suffering to the mice used for cancer xenograft experiments. Zebrafish (Danio rerio) embryos, however, offer many advantages as a model system for studying the complex, multi-step processes involved during cancer metastasis. This article describes a detailed method for the analysis of human cancer cell invasion and metastasis in zebrafish embryos before they reach protected status at 5 days post fertilisation. Results demonstrate that human cancer cells actively invade within a zebrafish microenvironment, and form metastatic tumours at secondary tissue sites, suggesting that the mechanisms involved during the different stages of metastasis are conserved between humans and zebrafish, supporting the use of zebrafish embryos as a viable model of human cancer metastasis. We suggest that the embryonic zebrafish xenograft model of human cancer is a tractable laboratory model that can be used to understand cancer biology, and as a direct replacement of mice for the analysis of drugs that target cancer invasion and metastasis.

Role of exosomes in diagnosis and therapy of prostate cancer

2020 ◽  
Vol 28 (3) ◽  
pp. 399-405
Author(s):  
Fabrizio Fontana ◽  
Olga A. Babenko
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Biological Fluids ◽  
Diagnosis And Treatment ◽  
Diagnosis And Therapy ◽  
The Future ◽  
Important Direction ◽  
Potential Biomarkers

Aim of this letter is to attract the attention of journal readers to the study of exosomes as an important direction in the development of Oncology, in particular, in the diagnosis and treatment of prostate cancer. Exosomes are produced by tumor cells and regulate proliferation, metastasis, and the development of chemoresistance. Their extraction from biological fluids allows further use of these vesicles as potential biomarkers of prostate cancer. In the future, exosomes can be successfully used in the delivery of drugs and other anti-tumor substances to cancer cells.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

The Potential of Milk-derived Exosomes for Drug Delivery

2020 ◽  
Vol 17 ◽  
Author(s):  
Shuyuan Li ◽  
Yue Tang ◽  
Yushun Dou
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Drug Loading ◽  
Drug Carriers ◽  
Current Application ◽  
Therapeutic Benefits ◽  
Loading Methods

Background: Exosomes, one of the extracellular vesicles, are widely present in all biological fluids and play an important role in intercellular communication. Because of its hydrophobic lipid bilayer and aqueous hydrophilic core structure, it is considered a possible alternative to liposome drug delivery systems. Not only do they protect the cargo like liposomes during delivery, they are less toxic and better tolerated. However, due to the lack of sources and methods for obtaining enough exosomes, the therapeutic application of exosomes as drug carriers is limited. Methods: A literature search was performed using the ScienceDirect and PubMed electronic databases to obtain information from published literature on milk exosomes related to drug delivery. Results: Here, we briefly reviewed the current knowledge of exosomes, expounded the advantages of milk-derived exosomes over other delivery vectors, including a higher yield, the oral delivery characteristic and additional therapeutic benefits. The purification and drug loading methods of milk exosomes, and the current application of milk exosomes were also introduced. Conclusion: The emergence of milk-derived exosomes is expected to break through the limitations of exosomes as therapeutic carriers of drugs. We hope to raise awareness of the therapeutic potential of milk-derived exosomes as a new drug delivery system.

Synthesis and Biological Evaluation of Novel Osthol Derivatives as Potent Cytotoxic Agents

2019 ◽  
Vol 15 (2) ◽  
pp. 138-149
Author(s):  
Saleem Farooq ◽  
Javid A. Banday ◽  
Aashiq Hussain ◽  
Momina Nazir ◽  
Mushtaq A. Qurishi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Natural Product ◽  
Cancer Therapeutics ◽  
Inhibitory Effect ◽  
Biological Evaluation ◽  
Negative Control ◽  
Normal Breast ◽  
Cytotoxic Agents ◽  
Breast Epithelial Cell ◽  
Exciting Field

Background: Natural product, osthol has been found to have important biological and pharmacological roles particularly having inhibitory effect on multiple types of cancer. Objective: The unmet needs in cancer therapeutics make its derivatization an important and exciting field of research. Keeping this in view, a whole new series of diverse analogues of osthol (1) were synthesized. Method: All the newly synthesized compounds were made through modification in the lactone ring as well as in the side chain of the osthol molecule and were subjected to anti-proliferative screening through 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) against four different human cancers of diverse origins viz. Colon (Colo-205), lung (A549), Leukemia (THP- 1) and breast (MCF-7) including SV40 transformed normal breast epithelial cell (fR-2). Results: Interestingly, among the tested molecules, most of the analogs displayed better antiproliferative activity than the parent Osthol 1. However, among all the tested analogs, compound 28 exhibited the best results against leukemia (THP1) cell line with IC50 of 5µM.Compound 28 induced potent apoptotic effects and G1 phase arrest in leukemia cancer cells (THP1). The population of apoptotic cells increased from 13.8% in negative control to 26.9% at 8μM concentration of 28. Compound 28 also induced a remarkable decrease in mitochondrial membrane potential (ΛΨm) leading to apoptosis of the cancer cells. Conclusion: A novel series of molecules derived from natural product osthol were synthesized, wherein compound 28 was found to be most effective against leukemia and with 10 fold less toxicity against normal cells. The compound induced cancer inhibition mainly through apoptosis and thus has a potential in cancer therapeutics.

scholarly journals Arsenic nano complex induced degradation of YAP sensitized ESCC cancer cells to radiation and chemotherapy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Wei Zhou ◽  
Meiyue Liu ◽  
Xia Li ◽  
Peng Zhang ◽  
Jiong Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Radiation Therapy ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Xenograft Model ◽  
Ros Production ◽  
Protective Effects ◽  
Migration Ability ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

Abstract Background Increased reactive oxygen species (ROS) production by arsenic treatment in solid tumors showed to be effective to sensitize cancer cells to chemotherapies. Arsenic nano compounds are known to increase the ROS production in solid tumors. Methods In this study we developed arsenic–ferrosoferric oxide conjugated Nano Complex (As2S2–Fe3O4, AFCNC) to further promote the ROS induction ability of arsenic reagent in solid tumors. We screen for the molecular pathways that are affect by arsenic treatment in ESCC cancer cells. And explored the underlying molecular mechanism for the arsenic mediated degradations of the key transcription factor we identified in the gene microarray screen. Mouse xenograft model were used to further verify the synthetic effects of AFCNC with chemo and radiation therapies, and the molecular target of arsenic treatment is verified with IHC analysis. Results With gene expression microarray analysis we found Hippo signaling pathway is specifically affected by arsenic treatment, and induced ubiquitination mediated degradation of YAP in KYSE-450 esophageal squamous cell carcinoma (ESCC) cells. Mechanistically we proved PML physically interacted with YAP, and arsenic induced degradation PML mediated the degradation of YAP in ESCC cells. As a cancer stem cell related transcription factor, YAP 5SA over expressions in cancer cells are correlated with resistance to chemo and radiation therapies. We found AFCNC treatment inhibited the increased invasion and migration ability of YAP 5SA overexpressing KYSE-450 cells. AFCNC treatment also effectively reversed protective effects of YAP 5SA overexpression against cisplatin induced apoptosis in KYSE-450 cells. Lastly, with ESCC mouse xenograft model we found AFCNC combined with cisplatin treatment or radiation therapy significantly reduced the tumor volumes in vivo in the xenograft ESCC tumors. Conclusions Together, these findings suggested besides ROS, YAP is a potential target for arsenic based therapy in ESCC, which should play an important role in the synthetic effects of arsenic nano complex with chemo and radiation therapy.

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