Amitozyn Impairs Chromosome Segregation and Induces Apoptosis via Mitotic Checkpoint Activation

Herman, Bastien; Aldrian, Gudrun; Potopalsky, A. I.; Chroboczek, Jadwiga; Tcherniuk, Sergey

doi:10.1371/journal.pone.0057461

Cited by 10 publications

(8 citation statements)

References 54 publications

(54 reference statements)

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“…Cell lysates were prepared as described previously [21]. Equal portions of protein (30 μg) were separated by SDS/PAGE, electrotransferred onto the nitrocellulose membrane and treated with the appropriate primary Ab diluted 1:1000.…”

Section: Methodsmentioning

confidence: 99%

Pgp efflux pump decreases the cytostatic effect of CENP-E inhibitor GSK923295

Tcherniuk

Oleinikov

2015

Cancer Letters

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Section: Methodsmentioning

confidence: 99%

Pgp efflux pump decreases the cytostatic effect of CENP-E inhibitor GSK923295

Tcherniuk

Oleinikov

2015

Cancer Letters

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“…The semi-synthetic drug amitozyn was prepared as described previously at a concentration of 25 mg/mL [ 15 ]. CQ, pyrimethamine, ART, monoclonal mouse anti-α-tubuline (T9026), and polyclonal anti-γ-tubuline antibodies (T3559) were purchased from Sigma.…”

Section: Methodsmentioning

confidence: 99%

“…Obtained results demonstrate that amitozyn possesses anti-malarial activity and inhibits in vitro blood stage growth of P. falciparum . Earlier, it has been shown that amitozyn is an effective anticancer drug, which acts as a microtubule modulator [ 15 ]. In this work the microtubule depolymerization effect of amitozyn was observed at different blood stages of P. falciparum, which could be the principal cause of its anti-malarial effect.…”

Section: Introductionmentioning

confidence: 99%

Anti-malarial effect of semi-synthetic drug amitozyn

Tcherniuk

Chesnokova

Oleinikov

et al. 2015

Malar J

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BackgroundMalaria caused by Plasmodium falciparum is the most virulent form of malaria, leading to approximately a half million deaths per year. Chemotherapy continues to be a key approach in malaria prevention and treatment. Due to widespread parasite drug resistance, identification and development of new anti-malarial compounds remains an important task of malarial parasitology. The semi-synthetic drug amitozyn, obtained through alkylation of major celandine (Chelidonium majus) alkaloids with N,N′N′-triethylenethiophosphoramide (ThioTEPA), is a widely used Eastern European folk medicine for the treatment of various tumours. However, its anti-malarial effect has never been studied.MethodsThe anti-malarial effects of amitozyn alone and in combination with chloroquine, pyrimethamine and artemisinin on the blood stages of P. falciparum were analysed. The cytostatic effects of amitozyn on parasites and various cancerous and non-cancerous human cells were compared and their toxic effects on unparasitized human red blood cells were analysed.ResultsObtained results demonstrate that amitozyn effectively inhibits the growth of blood-stage parasites with IC50 9.6 ± 2, 11.3 ± 2.8 and 10.8 ± 1.8 μg/mL using CS2, 3G8 and NF54 parasite lines, respectively. The median IC50 for 14 tested human cell lines was 33–152 μg/mL. Treatment of uninfected red blood cells with a high dose of amitozyn (500 μg/mL) did not change cell morphology, demonstrating its non-toxicity for erythrocytes. The synergistic impact of the amitozyn/chloroquine combination was observed at growth inhibition levels of 10–80 %, while demonstrating a nearly additive effect at a growth inhibition level of 90 %. The combination of amitozyn with pyrimethamine has a synergistic effect at growth inhibition levels of 10–70 % and a nearly additive effect at a growth inhibition level of 90 %. The synergistic anti-malarial effect of the amitozyn/artemisinin combination was observed at growth inhibition levels of 10–40 % and a nearly additive effect at growth inhibition levels of 50–90 %.ConclusionsThese in vitro results suggest that the semi-synthetic drug amitozyn, typically used for the treatment of tumours, is a potential anti-malarial candidate and warrants more detailed laboratory and pre-clinical investigations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0952-4) contains supplementary material, which is available to authorized users.

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“…In this case most of cancer cells died through apoptosis -the natural aging process. [5] Inherited resistance effect in rats race cured from Heren cancer was determined.…”

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Molecular Genetic Recovery of the Environment and Humans – The Way to Increase the Profitability of Agriculture and the Welfare of People

Potopalsky¹,

Bolsunova²,

Zaika³

2016

GISAP:BVMAS

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This article deals with new unique biotechnologies aimed at human health promotion and wellbeing of people on Earth. The authors present results of over 50-years-long research on development of original methods.The task of careful and responsible regulatory impact upon healthy and sick organisms of living beings is no longer the concern of scientists only. By thousands years of history humanity has certainly proved to have inexhaustible self-regulating abilities and reserves of wild Nature.The problems of regulation of biological processes under conditions of good health and disease, especially under the so-called stress conditions and induced fatal diseases, have been studied. The technology has been elaborated to struggle against the widespread viral diseases with the drug izatizon, which has a broad spectrum of antiviral activity, including the DNA-and RNA-containing viruses, viral and microbial associations. Unique anticancer drug amitozyin with immunomodulating and antiviral action is perhaps the world's only preparation that does not cause side effects at absolute anticancer effectiveness. The role of natural biologically active substances, their analogues and modifi cation products in the human and environmental molecular-genetic sanitation can hardly be overestimated.

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Amitozyn Impairs Chromosome Segregation and Induces Apoptosis via Mitotic Checkpoint Activation

Cited by 10 publications

References 54 publications

Pgp efflux pump decreases the cytostatic effect of CENP-E inhibitor GSK923295

Pgp efflux pump decreases the cytostatic effect of CENP-E inhibitor GSK923295

Anti-malarial effect of semi-synthetic drug amitozyn

Molecular Genetic Recovery of the Environment and Humans – The Way to Increase the Profitability of Agriculture and the Welfare of People

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