Activation of Auutophagyin Tumor Cells by Synthetic Monophenol Antioxidants: Dependence on Structure and Concentration

Menshchikova, E. B.; Чечушков, А. В.; Кожин, П. М.; Kholshin, S. V.; Кандалинцева, Н. В.; Мартинович, Г. Г.; Зенков, Н. К.

doi:10.15688/jvolsu11.2018.1.10

Cited by 3 publications

(2 citation statements)

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“…It has been established that, in addition to antioxidant and detoxifying effects (Milaeva et al 2006), phenols and polyphenols can independently exhibit selective toxicity against tumor cells, the data was obtained from in vitro experiments (Gaynutdinov et al 2018). Synthetic monophenolic antioxidants activate autophagy and apoptotic processes in tumor cells (Menshchikova et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the pharmacological activity of hybrid organotin compounds in a B16 melanoma model in the classical and metronomic administration modes

Додохова¹,

Сафроненко²,

Котиева³

et al. 2022

RRP

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Introduction: In modern medical chemistry, much attention is paid to the search for new antimetastatic agents based on metal compounds. Organotin compounds promise to be good candidates as the treatment of malignant neoplasms. In order to reduce a possible nonspecific toxic effect of tin compounds and to expand the intended therapeutic use, the paper presents hybrid tin (IV) complexes with Sn-S bond containing a fragment of 2,6-di-tert-butylphenol. The aim of the study was to evaluate the antitumor and antimetastatic effects of bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethylolol (Me3) and (3,5-di-tert-butyl-4-hydroxyphenylthiolate) triphenylolol (Me5) in a model of transplanted melanoma tumor in B16 mice in classical and metronomic administration mode. Materials and methods: The efficacy of organotin compounds was studied in a model of a transplanted tumor with spontaneous metastasis of C57Bl/6 (female) melanoma B16 mice using the following indicators: average life expectancy, inhibition of tumor growth by weight, tumor mass, and metastasis inhibition index. Results and discussion: The most pronounced antimetastatic effect (54% and 36%) is achieved with a five-fold intraperitoneal injection of Me3 and Me5 at the total doses of 375 mg/kg and 250 mg/kg. The comparable results of the efficacy were obtained in the classical and metronomic modes of the injection of hybrid organotin compounds. With an increase in the injected dose, there is an effect of activating the tumor process with the generalized metastasis. Conclusion: Bis dimethylolol (Me3) and triphenylolol (Me5) compounds demonstrate both a pronounced antimetastatic activity and a multidirectional effect on the growth of the primary focus and the metastasis in lungs, depending on an injected dose.

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Section: Introductionmentioning

confidence: 99%

Evaluation of the pharmacological activity of hybrid organotin compounds in a B16 melanoma model in the classical and metronomic administration modes

Додохова¹,

Сафроненко²,

Котиева³

et al. 2022

RRP

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show abstract

“…The choice of 2,6-di-tret-butylphenol group is based on our previous studies that demonstrated a potent antioxidant property of this group as well as an antitumor efficacy of substituted phenol derivatives (Gaynutdinov et al 2018;Menshchikova et al 2018). 2,6-di-tret-butylphenols are biomimetics of natural antioxidants (α-tocopherol).…”

Section: Introductionmentioning

confidence: 99%

Impact of organotin compounds on the growth of epidermoid Lewis carcinoma

Додохова¹,

Сафроненко²,

Котиева³

et al. 2021

RRP

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Introduction: Search for new compounds with a broad antitumor and antimetastatic potency due to multiple targeting remains important in medicinal chemistry, pharmacology and oncology. We report the efficacy of hybrid organotin agents bis-(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (Ме3) and (3,5-di-tert-butyl-4-hydroxyphenylthiolate) triphenyltin (Ме5). Materials and methods: The compounds were administered to mice bearing the spontaneously metastatic epidermoid Lewis lung carcinoma (LLC). The efficacy of the treatment was evaluated by mean life span, percentage of tumor growth inhibition, number of lung metastases, frequency of metastasis, tumor weight 21 days after tumor cell inoculation, and a degree of lung damage according to the method of D. Tarin and J.E. Price. Results and discussion: For new organotin compounds containing an antioxidant protective fragment of 2,6-di-tert-butylphenol, moderate antitumor and pronounced antimetastatic effects were revealed in the Lewis model of epidermoid lung carcinoma; more active for Me5. Some features of the development of the process of metastasis were recorded with the introduction of various doses of hybrid organotin compounds. Conclusion: Substances Ме3 and Ме5 possess specific activity on the model under investigation, which allows one to suggest these organotins as promising series of antitumor and antimetastatic agents with multiple targeting mode of action.

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Effect of Hybrid Organotin Compounds at the Maximum Effective Dose on the Growth and Metastasis Activity of B16 Melanoma in C57bl/6 Mice

Додохова

Котиева

Сафроненко

et al. 2022

Crimea Journal of Experimental and Clinical Medicine

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Metastasis is a complex multicomponent process that largely determines the effect of the tumor process on the body. The study of indicators of changes in the activity of metastasis under the influence of new antitumor agents is one of the most important tasks of experimental pharmacology and oncology. The effect of the organotin compounds (OOS) bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethylolol (Me3) and (3,5-di-tert-butyl-4-hydroxyphenylthiolate) triphenylolol (Me5) was studied at the maximum effective total doses of 375 mg/kg and 250 mg/kg, respectively, on a model of a spontaneously metastasizing transferable tumor melanoma B16. Both compounds showed a high antimeta- static effect, more pronounced for the dialkyl organic compound.

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Activation of Auutophagyin Tumor Cells by Synthetic Monophenol Antioxidants: Dependence on Structure and Concentration

Abstract: The present research is devoted to the study of the relationship between the structure of the original synthetic monophenolic antioxidants and their ability to influence the activity of autophagy in tumor cells.

Cited by 3 publications

References 1 publication

Evaluation of the pharmacological activity of hybrid organotin compounds in a B16 melanoma model in the classical and metronomic administration modes

Evaluation of the pharmacological activity of hybrid organotin compounds in a B16 melanoma model in the classical and metronomic administration modes

Impact of organotin compounds on the growth of epidermoid Lewis carcinoma

Effect of Hybrid Organotin Compounds at the Maximum Effective Dose on the Growth and Metastasis Activity of B16 Melanoma in C57bl/6 Mice

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