Search results for "UNAT"

Toxicity of the antimalarial artemisinin and its dervatives.

2010

As long as no effective malaria vaccine is available, chemotherapy belongs to the most important weapons fighting malaria. One of the most promising new drug developments is the sesquiterpene artemisinin (ARS) and its derivatives, e.g., artemether, arteether, and sodium artesunate. Large clinical studies and meta-analyses did not show serious side effects, although proper monitoring of adverse effects in developing countries might not be a trivial task. There is a paucity of large-scale clinical trials suitable to detect rare but significant toxicity. Therefore, a final and definitive statement on the safety of artemisinins still cannot be made. In contrast, animal experiments show consider…

Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron

2004

Abstract Iron(II) heme-mediated activation of the peroxide bond of artemisinins is thought to generate the radical oxygen species responsible for their antimalarial activity. We analyzed the role of ferrous iron in the cytotoxicity of artemisinins toward tumor cells. Iron(II)–glycine sulfate (Ferrosanol) and transferrin increased the cytotoxicity of free artesunate, artesunate microencapsulated in maltosyl-β-cyclodextrin, and artemisinin toward CCRF-CEM leukemia and U373 astrocytoma cells 1.5- to 10.3-fold compared with that of artemisinins applied without iron. Growth inhibition by artesunate and ferrous iron correlated with induction of apoptosis. Cell cycle perturbations by artesunate an…

Artesunate Activates Mitochondrial Apoptosis in Breast Cancer Cells via Iron-catalyzed Lysosomal Reactive Oxygen Species Production

2011

The antimalarial agent artesunate (ART) activates programmed cell death (PCD) in cancer cells in a manner dependent on the presence of iron and the generation of reactive oxygen species. In malaria parasites, ART cytotoxicity originates from interactions with heme-derived iron within the food vacuole. The analogous digestive compartment of mammalian cells, the lysosome, similarly contains high levels of redox-active iron and in response to specific stimuli can initiate mitochondrial apoptosis. We thus investigated the role of lysosomes in ART-induced PCD and determined that in MCF-7 breast cancer cells ART activates lysosome-dependent mitochondrial outer membrane permeabilization. ART impac…

La obra de Galdós en las traducciones italianas

2020

From the translation of Marianela (1880), the Italian reception of the works of Benito Pérez Galdós through translations does not present a very satisfactory situation, but rather uneven, especially if we take into account the production of contemporary translations to the Canarian writer or in the decades immediately after his disappearance, with some emblematic cases of manipulation with a very partial and censored translation such as that of Fortunata e Giacinta (1926), framed in the Fascist Ventennio, although it was the first translation into a foreign language of the Galdosian masterpiece. This study aims to recover and organize the panorama of translations into Italian of Galdós's na…

Betrug und Täuschung in der Literatur des späten 15. und des frühen 16. Jahrhunderts

2022

‘Donne bibliche da Venanzio Fortunato ad un anonimo compilatore anglosassone’

1991

LUSSAZIONE DISSOCIATA DEL SEMILUNARE E DELLE OSSA DEL CARPO: CASE REPORT

2014

Artesunate derived from traditional Chinese medicine induces DNA damage and repair.

2008

Abstract Artesunate is a semisynthetic derivative from artemisinin, a natural product from the Chinese herb Artemisia annua L. It exerts antimalarial activity, and, additionally, artemisinin and its derivatives are active against cancer cells. The active moiety is an endoperoxide bridge. Its cleavage leads to the formation of reactive oxygen species and carbon-centered radicals. These highly reactive molecules target several proteins in Plasmodia, which is thought to result in killing of the microorganism. DNA damage induced by artemisinins has not yet been described. Here, we show that artesunate induces apoptosis and necrosis. It also induces DNA breakage in a dose-dependent manner as sho…

Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells.

2011

Breast cancer is the most common cancer and the second leading cause of cancer death in industrialized countries. Systemic treatment of breast cancer is effective at the beginning of therapy. However, after a variable period of time, progression occurs due to therapy resistance. Artesunate, clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity offering a role as novel candidate for cancer chemotherapy. We analyzed the anti-tumor effects of artesunate in metastasizing breast carcinoma in vitro and in vivo. Unlike as expected, artesunate induced resistance in highly metastatic human breast cancer cells MDA-MB-231. Likewise acquired resistance led to abol…

Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells.

2011

Abstract Artesunate, the active agent from Artemisia annua L. used in the traditional Chinese medicine, is being applied as a first-line drug for malaria treatment, and trials are ongoing that include this drug in cancer therapy. Despite increasing interest in its therapeutic application, the mode of cell killing provoked by artesunate in human cells is unknown. Here, we show that artesunate is a powerful inducer of oxidative DNA damage, giving rise to formamidopyrimidine DNA glycosylase–sensitive sites and the formation of 8-oxoguanine and 1,N6-ethenoadenine. Oxidative DNA damage was induced in LN-229 human glioblastoma cells dose dependently and was paralleled by cell death executed by ap…