Bioflavonoids cause DNA double-strand breaks and chromosomal translocations through topoisomerase II-dependent and -independent mechanisms

Publication date: Available online 22 January 2020Source: Mutation Research/Genetic Toxicology and Environmental MutagenesisAuthor(s): Donna Goodenow, Faith Emmanuel, Chase Berman, Mark Sahyouni, Christine RichardsonAbstractBioflavonoids have a similar chemical structure to etoposide, the well-characterized topoisomerase II (Top2) poison, and evidence shows that they also induce DNA double-strand breaks (DSBs) and promote genome rearrangements. The purpose of this study was to determine the kinetics of bioflavonoid-induced DSB appearance and repair, and their dependence on Top2. Cells were exposed to bioflavonoids individually or in combination in the presence or absence of the Top2 catalytic inhibitor dexrazoxane. The kinetics of appearance and repair of γH2AX foci were measured. In addition, the frequency of resultant MLL-AF9 breakpoint cluster region translocations was determined. Bioflavonoids readily induced the appearance of γH2AX foci, but bioflavonoid combinations did not act additively or synergistically to promote DSBs. Myricetin-induced DSBs were mostly reduced by dexrazoxane, while genistein and quercetin-induced DSBs were only partially, but significantly, reduced. By contrast, luteolin and kaempferol-induced DSBs increased with dexrazoxane pre-treatment. Sensitivity to Top2 inhibition correlated with a significant reduction of bioflavonoid-induced MLL-AF9 translocations. These data demonstrate that myricetin, genistein, and quercetin act most similar...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research

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Authors: Karamanou M Abstract Throughout history arsenic had a dual role as an ideal poison and as a remedy. Derived from the Greek word "arsenikón" meaning masculine or valiant, referring to its powerful activity, arsenic was prescribed since antiquity in mixtures and it was applied topically to treat cancer. In 17th century, the French physician Pierre Alliot (1610-1685) proposed a secret remedy for cancer treatment. His invention, known as Alliot's powder, gained popularity and it was also prescribed to queen mother Anne of Austria (1601-1666) who was suffering from breast cancer, without any ef...
Source: Journal of B.U.ON. - Category: Cancer & Oncology Tags: J BUON Source Type: research
Contributors : Piyush More ; Leszek WojnowskiSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensRecently approved cancer drugs remain out-of-reach to most patients due to prohibitive costs and only few produce clinically meaningful benefits. An untapped alternative is to enhance the efficacy and safety of existing cancer treatments. We hypothesized that the response to topoisomerase II poisons, the most successful group of cancer drugs, can be improved by considering treatment-associated transcript levels, taken as surrogates for protein expression. To this end, we analyzed transcriptome...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Authors: More P, Goedtel-Armbrust U, Shah V, Mathaes M, Kindler T, Andrade-Navarro MA, Wojnowski L Abstract Recently approved cancer drugs remain out-of-reach to most patients due to prohibitive costs and only few produce clinically meaningful benefits. An untapped alternative is to enhance the efficacy and safety of existing cancer drugs. We hypothesized that the response to topoisomerase II poisons, a very successful group of cancer drugs, can be improved by considering treatment-associated transcript levels. To this end, we analyzed transcriptomes from Acute Myeloid Leukemia (AML) cell lines treated with the top...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Publication date: Available online 15 May 2019Source: Mutation Research/Genetic Toxicology and Environmental MutagenesisAuthor(s): P. Gollapudi, V.S. Bhat, D.A. EastmondAbstractTopoisomerase II (topo II) inhibitors are commonly used as chemotherapy to treat multiple types of cancer, though their use is also associated with the development of therapy related acute leukemias. While the chromosome-damaging effects of etoposide, a topo II poison, have been proposed to act through a threshold mechanism, little is known about the chromosome damaging effects and dose responses for the catalytic inhibitors of the enzyme. The curre...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research
Joseph D. Romano1,2,3,4 and Nicholas P. Tatonetti1,2,3,4* 1Department of Biomedical Informatics, Columbia University, New York, NY, United States 2Department of Systems Biology, Columbia University, New York, NY, United States 3Department of Medicine, Columbia University, New York, NY, United States 4Data Science Institute, Columbia University, New York, NY, United States The discovery of new pharmaceutical drugs is one of the preeminent tasks—scientifically, economically, and socially—in biomedical research. Advances in informatics and computational biology have increased productivity at many stag...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusion and Perspectives Collectively, previous studies showed that numerous types of TCMs protect against AKI via different mechanisms of action, including inhibiting inflammation, cell apoptosis, necroptosis, ferroptosis, and restraining oxidative stress etc. These data support the potential application of these TCMs as novel therapeutic agents in treating patients with AKI. Although some TCMs have entered preclinical trials, it is essential to initiate pre-clinical pharmacologic and toxicologic trials and clinical trials to evaluate the efficacy and safety of TCMs usage. Moreover, considering that some TCMs are dele...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This study aimed to contribute to the need of finding new and more effective bioactive molecules against several of the earlier mentioned threats faced by human kind nowadays. For this, eighteen species from the Actinomycetales previously isolated from Erylus spp. sponges collected in Portuguese marine waters (Açores, Madeira, and continental shelf) were screened for antimicrobial, anti-cancer, anti-parasitic and anti-obesogenic activities. Materials and Methods Biological Material The bacteria under study belong to the order Actinomycetales within the phylum Actinobacteria and were isolated from marine sponges o...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
A new study shows how an arsenic oxide, in combination with an existing drug, can cure leukemia, and it may be able to also treat other types of cancer.
Source: Health News from Medical News Today - Category: Consumer Health News Tags: Cancer / Oncology Source Type: news
Discussion Flushing is usually thought of as a benign condition such as blushing, but can be quite irritating if it is frequent or persistent (i.e. menopausal hot flashes) or even pathologic (i.e. malignancy). “Flushing is a subjective and sensation of warmth that is accompanied by reddening of the skin anywhere on the body but favors the face, neck, and upper torso…. Flushing can be broadly divided into episodic or persistent. Episodic flashing is mediated by the release of endogenous vasoactive mediators or medications, while persistent flushing result in a fixed facial erythema with telangiectasias and cyan...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Abstract Arsenic and its various forms have been in use in ancient Chinese medicine for more than 2000 years. Arsenicals have gained importance for having remedial effects for various diseases from syphilis to cancer thus highlighting its role as a therapeutic agent even though it has been labelled as a potential 'poison'. The ability of arsenic, specifically arsenic trioxide, to treat acute promyelocytic leukaemia has radically changed the perception of this poison and has been the main factor for the re-emergence of this candidate to Western medicine for the treatment of leukaemia and other solid tumours. T...
Source: Journal of Biological Inorganic Chemistry : JBIC - Category: Chemistry Authors: Tags: J Biol Inorg Chem Source Type: research
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