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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In in vitro cytotoxicity studies, ellipticine has significant activity in nasopharyngeal carcinoma cell lines. A number of ellipticine analogues have been synthesized and studied in the clinic through the years. However, although some have been observed to induce remission of tumor growth, as a class they produce a high level of toxicity (e.g., nausea, vomiting, hypertension, cramp, severe fatigue, mouth dryness and mycosis of the tongue, and esophagus), and so none have progressed to the approval stage.
Mechanisms of Resistance to Antineoplastic Drugs
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
Philip J. Vickers, Alan J. Townsend, Kenneth H. Cowan
Cells also possess a complex array of drug-metabolizing enzymes which have a relatively broad substrate specificity and can therefore deactivate a wide range of drugs. These enzymes are traditionally classified into two general classes. Phase I drug-metabolizing enzymes, the majority of which are cytochrome P-450-dependent enzymes, in general catalyze the oxidation of substrates to more chemically reactive metabolites. These intermediates are often more toxic forms of these chemicals. While these enzyme activities convert carcinogens such as benzo(a)pyrene to more toxic intermediates, their role in the metabolism of anticancer drugs is less clear. However, the cytotoxic drug ellipticine is converted to a more toxic 9-hydroxy species by the phase I enzyme aryl hydrocarbon hydroxylase. Changes in the expression of this enzyme can result in resistance to ellipticine.20
Intelligent Nanomaterials for Medicine: Carrier Platforms and Targeting Strategies—State of the Art
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Georgette B. Salieb-Beugelaar, Marc Wolf, Roman Lehner, Kegang Liu, Stephan Marsch, Patrick Hunziker
Peptides can have lipophilic or hydrophilic properties based on their amino acid composition and can therefore be used to construct amphiphilic molecules that form nanostructures by self-assembly [132–134]. Design considerations of these biopolymers for drug carriers are similar to other biocompatible polymers, but should take into account that peptides may act as strong immunogens and that the body already contains several lines of defense against foreign proteins and peptidic structures like virus capsids. In addition, a variety of peptidases exist in the body; if a system is preclinically developed for later clinical use in man, species differences in peptidase expression needs to be carefully considered. Virus self-assembly can act as an inspiration to build hollow or solid peptidic nanostructures [135, 136]. Bawa et al. showed enhanced cellular delivery and activity of the anticancer drug ellipticine to human lung carcinoma A549 cells using self-assembling peptide-based nanoparticles [137]. Naskar et al. presented the formation of multivesicular structures from self-assembling peptides, depicting sensitivity upon exposure to calcium ions leading to vesicular disruption. This intelligent sensing/switching functionality, allows cargo release suited for medically relevant payloads [138]. However, a natural extension of peptide-based systems is the exploitation of biologic peptide functions like their use as receptor ligands or enzymatic activity, naturally leading to nanomaterials with complex or switchable functionalities. Clinically, peptidic systems have entered clinical trials dominantly as nanoplatforms for vaccines offering multivalency as a potent immune system stimulant.
3D self-assembled nanocarriers for drug delivery
Published in Drug Metabolism Reviews, 2023
Hossein Karballaei Mirzahosseini, Mojgan Sheikhi, Farhad Najmeddin, Mehrnoosh Shirangi, Mojtaba Mojtahedzadeh
It has been demonstrated that the self-assembled nanofiber structures made from EAK peptides are capable of encapsulating the anticancer drug ellipticine for delivery. Two approaches were used to examine the self-assembly and drug delivery applications. The first one is the UV-based approach. The results of this method revealed that the conjugation between the peptide and the anticancer drug ellipticine was based on electrostatic interactions. The effectiveness of medication loading into peptide self-assembled nanostructures may also be evaluated using this method. The second method is to make use of fluorescence technology, which can monitor the conjugation procedure and its efficiency. We were able to monitor the fluorescence properties and calculate the dosages of the anticancer drug ellipticine based on the results during the whole self-assembly and delivery process. The self-assembled nanofibers, which contain the anticancer drug ellipticine, were also found to be more successful at treating cancer while they were in their protonated state in vitro testing than when they were in their crystalline form. Along with these EAK peptide self-assembled nanostructures and the two encapsulating approaches, other anticancer medications may be used in drug delivery for cancer therapy (Ji et al. 2016).
In vitro cytotoxicity of polyphenols from Datura innoxia aqueous leaf-extract on human leukemia K562 cells: DNA and nuclear proteins as targets
Published in Drug and Chemical Toxicology, 2020
Elham Chamani, Roshanak Ebrahimi, Khatereh Khorsandi, Azadeh Meshkini, Asghar Zarban, Gholamreza Sharifzadeh
Potent natural antioxidants change chromatin either by directly affecting the DNA backbone or by targeting the proteins related to it (Russo et al. 2017). It has been reported that dietary polyphenols such as curcumin, resveratrol, and catechin can influence transcription through posttranslational modifications of histones which change the structure of chromatin (Russo et al. 2017). Banerjee et al. (2017) investigated the effect of ellipticine, a plant alkaloid, on chromatin and nucleosomal DNA. Their results revealed that ellipticine interacted with chromatin components, especially core histone proteins. Recent studies have reported on the toxic effect of D. stromonium on breast (MDA-MB-231), head, neck (FaDu), and lung (A549) cancer cell lines (Maheshwari et al. 2013). They showed that its lectin and agglutinin contents had inhibitory effects on head, neck, lungs, and breast cancer cells and reduced the proliferation of C6 glioma cells (Sasaki et al. 2002).
Induction of adaptive immune response by self-aggregating peptides
Published in Expert Review of Vaccines, 2018
Jesus Zepeda-Cervantes, Luis Vaca
There are few reports of how SAPs that form NPs are taken up by cells. Bawa et al. reported that EAK16-II (n-AEAEAKAKAEAEAKAK-c) can stabilize ellipticine (EPT), a hydrophobic anticancer drug, forming NPs, which are taken up by human lung carcinoma A549 cells through caveolae-dependent pathway. They also showed that nanoformulation was rapidly uptake in 2 min, but with microformulation, very low levels of EPT uptake were observed over a 10-min period [87]. This could occur in a similar manner with APCs, since DCs can uptake protein particles of 20–200 nm better than microparticles [88].