Mill. (Cs), a plant traditionally employed in nutrition and to treat various respiratory and gastrointestinal infections, possesses cancer chemopreventive characteristics. In particular, Cs bark extract previously demonstrated antiproliferative and pro-apoptotic activities against a leukemic lymphoblastic cell line.
View Article and Find Full Text PDFMTTA, also known as mephtetramine, is a stimulant novel psychoactive substance characterized by a simil-cathinonic structure. To date, little has been studied on its pharmaco-toxicological profile, and its genotoxic potential has never been assessed. In order to fill this gap, the aim of the present work was to evaluate its genotoxicity on TK6 cells in terms of its ability to induce structural and numerical chromosomal aberrations by means of a cytofluorimetric protocol of the "In Vitro Mammalian Cell Micronucleus (MN) test".
View Article and Find Full Text PDFNeuroblastoma cells highly express the disialoganglioside GD2, a tumor-associated carbohydrate antigen, which is also expressed in neurons, skin melanocytes, and peripheral nerve fibers. Immunotherapy with monoclonal anti-GD2 antibodies has a proven efficacy in clinical trials and is included in the standard treatment for children with high-risk neuroblastoma. However, the strong neuro-toxicity associated with anti-GD2 antibodies administration has hindered, until now, the possibility for dose-escalation and protracted use, thus restraining their therapeutic potential.
View Article and Find Full Text PDFPharmaceuticals (Basel)
November 2022
Little is known about the pharmacological activity of Ammodaucus leucotrichus Coss. & Dur., a small annual species that grows in the Saharan and sub-Saharan countries.
View Article and Find Full Text PDFThree fentanyl analogues Acrylfentanyl, Ocfentanyl and Furanylfentanyl are potent, rapid-acting synthetic analgesics that recently appeared on the illicit market of new psychoactive substances (NPS) under the class of new synthetic opioids (NSO). Pharmacotoxicological data on these three non-pharmaceutical fentanyl analogues are limited and studies on their genotoxicity are not yet available. Therefore, the aim of the present study was to investigate this property.
View Article and Find Full Text PDFAutophagy is a fundamental catabolic process of cellular survival. The role of autophagy in cancer is highly complex: in the early stages of neoplastic transformation, it can act as a tumor suppressor avoiding the accumulation of proteins, damaged organelles, and reactive oxygen species (ROS), while during the advanced stages of cancer, autophagy is exploited by cancer cells to survive under starvation. 6-(Methylsulfonyl) hexyl isothiocyanate (6-MITC) is the most interesting compound in the rizhome.
View Article and Find Full Text PDFThe novel psychoactive substance (NPS) 4-Methyl-5-(4-methylphenyl)-4,5-dihydroxazol-2-amine (4,4'-DMAR) shows psychostimulant activity. Data on the acute toxicity of 4,4'-DMAR are becoming increasingly available, yet the long-term effects are still almost unknown. In particular, no data on genotoxicity are available.
View Article and Find Full Text PDFA genotoxicological study was carried out on a substance-based medical device (SMD) containing anthraquinones in order to evaluate its potential mutagenic effect. The "In Vitro Mammalian Cell Micronucleus Test" was performed on human TK6 cells by flow cytometry. Cultures were treated with concentrations of SMD tested in the range of 0-2 mg/mL for short treatment time (3 h) both in the absence and presence of an exogenous metabolic activation system, followed by a recovery period in fresh medium (23 h) and for extended treatment time (26 h) without an exogenous metabolic activation system.
View Article and Find Full Text PDFMexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent.
View Article and Find Full Text PDFPsychedelic and stimulating phenethylamines belong to the family of new psychoactive substances (NPS). The acute toxicity framework has begun to be investigated, while studies showing genotoxic potential are very limited or not available. Therefore, in order to fill this gap, the aim of the present work was to evaluate the genotoxicity by treating TK6 cells with 2C-H, 2C-I, 2C-B, 25B-NBOMe, and the popular 3,4-Methylenedioxymethylamphetamine (MDMA).
View Article and Find Full Text PDF6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), is the main bioactive compound present in rhizome. Several scientific studies have shown that 6-MITC possesses interesting antimicrobial, anti-inflammatory, antiplatelet and antioxidant properties which therefore suggested us it could have an interesting chemopreventive potential. In a recent publication, we demonstrated, in two different leukemia cell lines, its ability to modulate several mechanisms supporting its antitumor activity.
View Article and Find Full Text PDFNovel Psychoactive Substances (NPS) include several classes of substances such as synthetic cannabinoids (SCBs), an emerging alternative to marijuana, easily purchasable on internet. SCBs are more dangerous than Δ-Tetrahydrocannabinol as a consequence of their stronger affinities for the CB and CB receptors, which may result in longer duration of distinct effects, greater potency, and toxicity. The information on SCBs cytotoxicity, genotoxicity, mutagenicity, and long-term effects is scarce.
View Article and Find Full Text PDFCellular senescence is a fundamental process that may play positive or detrimental roles for the organism. It is involved in tissue development and in tumor prevention although during aging is becoming a detrimental process contributing to the decline of tissue functions. In previous investigations, we have uncovered a better capacity to detect DNA damage in cells from long-lived mammals.
View Article and Find Full Text PDFOxid Med Cell Longev
January 2019
Sulforaphane, a biologically active isothiocyanate compound extracted from cruciferous vegetables, has been shown to exert cytotoxic effects on many human cancer cells, including leukemia. However, the exact molecular mechanisms behind the action of sulforaphane in hematological malignancies are still unclear. Like other cancer cells, leukemia cells produce high level of reactive oxygen species; in particular, hydrogen peroxide derived from Nox family is involved in various redox signal transduction pathways, promoting cell proliferation and survival.
View Article and Find Full Text PDFBackground: The interest towards botanicals and plant extracts has strongly risen due to their numerous biological effects and ability to counteract chronic diseases development. Among these effects, chemoprevention which represents the possibility to counteract the cancerogenetic process is one of the most studied. The extracts of mushroom Meripilus giganteus (MG) (Phylum of Basidiomycota) showed to exert antimicrobic, antioxidant and antiproliferative effects.
View Article and Find Full Text PDFNumerous laboratory and epidemiological studies show that the risk of developing several types of cancer can be reduced with the employment of natural substances that act with multiple mechanisms. In this context, an important role is played by the isothiocyanates. Recently, 6-(methylsulfonyl)hexyl isothiocyanate (6-MITC), present in the root of , has stimulated the interest of researchers as a chemopreventive agent.
View Article and Find Full Text PDFCytometry B Clin Cytom
September 2018
Background: It is now recognized that mutational events play a key role in the development of pathological processes like cancer, cardiovascular, and neurodegenerative disease. Therefore, it is crucial to have Genetics Toxicology tests that allow rapid and accurate identification of the mutagenic potential of a xenobiotic. Currently the most widely used technique is the "In vitro mammalian cell micronucleus test" performed by optical microscopy, but some problems have been highlighted, including the number of cells analyzed, the high subjectivity of the reading at the microscope and the long analysis times.
View Article and Find Full Text PDFBackground: Chemoprevention represents the possibility to prevent, stop or reverse the cancerogenetic process. In this context the interest towards natural extracts and botanical drugs has constantly grown due to their phytochemical content. Castanea sativa Mill.
View Article and Find Full Text PDFCancer is a complex disease characterized by multiple genetic and molecular alterations involving transformation, deregulation of apoptosis, proliferation, invasion, angiogenesis, and metastasis. To grow, invade, and metastasize, tumors need host components and primary dysfunction in the tumor microenvironment, in addition to cell dysfunction, can be crucial for carcinogenesis. A great variety of phytochemicals have been shown to be potentially capable of inhibiting and modulating several relevant targets simultaneously and is therefore non-specific.
View Article and Find Full Text PDFAnticancer chemotherapy is strongly hampered by the low therapeutic index of most anticancer drugs and the development of chemoresistance. Therefore, there is a continued need for the identification of new molecular targets in order to selectively hit cancer cells. RNA has been recently validated as a cancer target by the use of different specific ligands and/or by different agents able to destroy its diverse forms.
View Article and Find Full Text PDFThis work was aimed at evaluating the cardioprotective effects of Castanea sativa Mill. (CSM) bark extract characterized in its phenolic composition by HPLC-DAD-MS analysis. The study was performed using primary cultures of neonatal rat cardiomyocytes to investigate the antioxidant and cytoprotective effects of CSM bark extract and isolated guinea pig left and right atria, left papillary muscle, and aorta to evaluate its direct effect on cholinergic and adrenergic response.
View Article and Find Full Text PDFExpert Opin Drug Metab Toxicol
July 2012
Introduction: Cancer is a complex disease, characterized by redundant aberrant signaling pathways as a result of genetic perturbations at different levels. Botanicals consist of a complex mixture of constituents and exhibit pharmacological effects by the interaction of many phytochemicals. The multitarget nature of botanicals could, therefore, be a relevant strategy to address the biological complexity that characterizes tumors.
View Article and Find Full Text PDFBackground: The isothiocyanate sulforaphane (SFN) possesses interesting anticancer activities. However, recent studies reported that SFN promotes the formation of reactive oxygen species (ROS) as well as DNA breakage.
Methodology/principal Findings: We investigated whether SFN is able to damage RNA, whose loss of integrity was demonstrated in different chronic diseases.
Isothiocyanates, occurring in many dietary cruciferous vegetables, show interesting chemopreventive activities against several chronic-degenerative diseases, including cancer, cardiovascular diseases, neurodegeneration, diabetes. The electrophilic carbon residue in the isothiocyanate moiety reacts with biological nucleophiles and modification of proteins is recognized as a key mechanism underlying the biological activity of isothiocyanates. The nuclear factor-erythroid-2-related factor 2 system, which orchestrates the expression of a wide array of antioxidant genes, plays a role in the protective effect of isothiocyanates against almost all the pathological conditions reported above.
View Article and Find Full Text PDF