Obvious and Hidden Reasons of Breast Cancer Cell Sensitivity to Antitumor RNase

Zelenikhin, P. V.; Pukhovskaya, Victoria; Garipov, Azat; Макеева, А В; Соколова, Е. А.; Ilinskaya, О. N.

doi:10.1007/s12668-016-0269-y

Cited by 7 publications

(6 citation statements)

References 15 publications

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“…Binase possesses selective toxicity toward certain tumor cells in vitro (Mitkevich et al, 2011, 2013, 2015; Zelenikhin P. et al, 2016; Zelenikhin P.V. et al, 2016; Makeeva et al, 2017) and in vivo (Mironova et al, 2013; Sen’kova et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…In some cases RNases catalytic activity may be an important factor for their cytotoxicity manifestation (Ilinskaya and Vamvakas, 1997; Makarov and Ilinskaya, 2003). However, the sensitivity of malignant breast cancer cells to binase apoptosis inducing effect was not shown to correlate with the level of cellular RNA catalytic degradation (Zelenikhin P. et al, 2016). This effect was also demonstrated for oncogene kit transformed cells (Mitkevich et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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Zeolites as Carriers of Antitumor Ribonuclease Binase

et al. 2019

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Natural and synthetic zeolites have many applications in biomedicine and nutrition. Due to its properties, zeolites can absorb therapeutically active proteins and release them under physiological conditions. In this study we tested the clinoptilolite, chabazite, and natrolite ability to be loaded by antitumor ribonuclease binase and the cytotoxicity of the obtained complexes. We found the optimal conditions for binase loading into zeolites and established the dynamic of its release. Cytotoxic effects of zeolite-binase complexes toward colorectal cancer Caco2 cells were characterized after 24 and 48 h of incubation with cells using MTT-test. Zeolites were toxic by itselfs and reduced cells viability by 30% (clinoptilolite), 40% (chabazite), and 70% (natrolite) after 48 h of incubation. Binase complexes with clinoptilolite as well as chabazite always demonstrated enhanced toxicity (up to 57 and 60% for clinoptilolite and chabazite, respectively) in comparison with binase and zeolites separately. Our results contribute to the perspective development of binase-based complexes for therapy of colorectal cancer for or the treatment of malignant skin neoplasms where the complexes can be used in pasty form.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Zeolites as Carriers of Antitumor Ribonuclease Binase

et al. 2019

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“…Фермент. В работе использовали биназу -гуанилспецифичную РНКазу Bacillus pumilus (молекулярная масса 12,3 кДа, pI=9,5, 109 аминокислотных остатков) в высоких концентрациях (100-500 мкг/мл), для которых ранее было установлено апоптоз-индуцирующее действие на ряде линий раковых клеток [4,6,7]. Биназа была изолирована как гомогенный белок из культуральной жидкости продуцента по методике, описанной Дудкиной с соавт.…”

Section: материалы и методыunclassified

“…Благодаря наличию селективного цитотоксического действия по отношению к злокачественным клеткам РНКаза Bacillus pumilus (биназа) может рассматриваться в качестве потенциального противоопухолевого агента. Установлено селективное действие биназы на клетки карциномы легкого человека линии А549 [4], фибробласты, экспрессирующие онкоген v-Ras [5], клетки миелоидного лейкоза [6], клетки рака молочной железы, в том числе и трижды негативные [7]. РНКазы в высоких концентрациях оказывают цитотоксическое [8,9] и генотоксическое действие [10], а также ингибируют активность Ca-зависимых калиевых каналов (К Са -каналов), приводя к апоптозу [11].…”

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Binase-Induced Changes of Tumor Cell Membranes

Zelenikhin

Горбунова

Beuerlein

et al. 2017

Moscow Univ. Biol.Sci. Bull.

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Экзогенные рибонуклеазы бацилл могут селективно индуцировать апоптоз злокачественных клеток. В работе проведен анализ способности рибонуклеазы Bacillus pumilusбиназы-индуцировать процессы, приводящие к динамическому нарушению целостности мембран клеток аденокарциномы легких человека линии А549. Охарактеризовано влияние фермента в различных концентрациях на состояние цитоплазматической мембраны клеток и мембран митохондрий. При помощи методов проточной цитофлуориметрии и флуоресцентной микроскопии установлено, что воздействие биназы приводит к нарушению нормального функционирования мембран обоих типов, причем вначале нарушения затрагивают мембраны митохондрий. Проведенное исследование позволило выявить и визуализировать этапы влияния биназы на мембранные структуры клеток-мишеней и подтвердить, что бактериальная РНКаза индуцирует апоптоз клеток-мишеней преимущественно по "внутреннему" (митохондриальному) пути.

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“…Over the last years, research interest in binase is constantly being increased because of selective cytotoxicity of this enzyme toward certain cancer cells. Binase inhibits proliferation of human leukemic Kasumi-1 cells, lung adenocarcinoma cells, ovarian and breast cancer cells ( Mitkevich et al, 2011 ; Cabrera-Fuentes et al, 2013 ; Garipov et al, 2014 ; Zelenikchin et al, 2016 ). The sensitivity of cancer cells to binase toxic action depends on the expression of ras, kit , AML1-ETO and FLT3 oncogenes, but does not depend on the expression of fms and src oncogenes ( Ilinskaya et al, 2001 , 2016 ; Mitkevich et al, 2011 , 2013b ).…”

Section: Introductionmentioning

confidence: 99%

Binase Immobilized on Halloysite Nanotubes Exerts Enhanced Cytotoxicity toward Human Colon Adenocarcinoma Cells

et al. 2017

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Many ribonucleases (RNases) are considered as promising tools for antitumor therapy because of their selective cytotoxicity toward cancer cells. Binase, the RNase from Bacillus pumilus, triggers apoptotic response in cancer cells expressing RAS oncogene which is mutated in a large percentage of prevalent and deadly malignancies including colorectal cancer. The specific antitumor effect of binase toward RAS-transformed cells is due to its direct binding of RAS protein and inhibition of downstream signaling. However, the delivery of proteins to the intestine is complicated by their degradation in the digestive tract and subsequent loss of therapeutic activity. Therefore, the search of new systems for effective delivery of therapeutic proteins is an actual task. This study is aimed to the investigation of antitumor effect of binase immobilized on natural halloysite nanotubes (HNTs). Here, we have developed the method of binase immobilization on HNTs and optimized the conditions for the enzyme loading and release (i); we have found the non-toxic concentration of pure HNTs which allows to distinguish HNTs- and binase-induced cytotoxic effects (ii); using dark-field and fluorescent microscopy we have proved the absorption of binase-loaded HNTs on the cell surface (iii) and demonstrated that binase-halloysite nanoformulations possessed twice enhanced cytotoxicity toward tumor colon cells as compared to the cytotoxicity of binase itself (iv). The enhanced antitumor activity of biocompatible binase-HNTs complex confirms the advisability of its future development for clinical practice.

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Obvious and Hidden Reasons of Breast Cancer Cell Sensitivity to Antitumor RNase

Cited by 7 publications

References 15 publications

Zeolites as Carriers of Antitumor Ribonuclease Binase

Zeolites as Carriers of Antitumor Ribonuclease Binase

Binase-Induced Changes of Tumor Cell Membranes

Binase Immobilized on Halloysite Nanotubes Exerts Enhanced Cytotoxicity toward Human Colon Adenocarcinoma Cells

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