Antitumor Activity of the Combination of Topotecan and Tyrosyl-DNA-Phosphodiesterase 1 Inhibitor on Model Krebs-2 Mouse Ascite Carcinoma

Antitumor Activity of the Combination of Topotecan and Tyrosyl-DNA-Phosphodiesterase 1 Inhibitor on Model Krebs-2 Mouse Ascite Carcinoma Full article

Journal

Molecular Biology
ISSN: 0026-8933

Output data

Year: 2021, Volume: 55, Number: 2, Pages: 273-277 Pages count : 5 DOI: 10.1134/S0026893321020060

Tags

Krebs-2 carcinoma; Tdp1 inhibitor; topoisomerase 1; topotecan; tyrosyl-DNA phosphodiesterase 1

Authors

Dyrkheeva N.S. ¹ , Zakharenko A.L. ¹ , Novoselova E.S. ² , Chepanova A.A. ^1,2 , Popova N.A. ^2,3 , Nikolin V.P. ³ , Luzina O.A. ⁴ , Salakhutdinov N.F. ⁴ , Ryabchikova E.I. ¹ , Lavrik O.I. ^1,2

Affiliations

1	Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation
2	Novosibirsk State University, Novosibirsk, 630090, Russian Federation
3	Federal Research Center Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation
4	Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation

Abstract: Topotecan is a cytostatic drug from the camptothecin group, it acts by inhibiting topoisomerase 1 (TOP1). Tyrosyl-DNA phosphodiesterase 1 (TDP1) is capable of interfering with the action of TOP1 inhibitors, reducing their therapeutic efficacy. Suppression of TDP1 activity may enhance the effects of topotecan. In this work, we investigated the effect of the antitumor drug topotecan alone and in combination with a TDP1 inhibitor, a hydrazinothiazole derivative of usnic acid, on Krebs-2 mouse ascites tumors. We have previously shown that this derivative efficiently inhibits TDP1. In the present work, we show that both topotecan and the TDP1 inhibitor have an antitumor effect when evaluated separately. The combination of topotecan and the TDP1 inhibitor additively reduces both the weight of the ascites tumor and the number of cells in ascites. In mice, the TDP1 inhibitor alone or in combination with topotecan eliminated the tumor cells. After the combined intraperitoneal administration of these two compounds, we observed cells in which lipid droplets occupied almost the entire cytoplasm and the accumulation of cell detritus, which was absent in the samples collected from mice treated with each compound separately. © 2021, Pleiades Publishing, Inc.

Dyrkheeva N.S. , Zakharenko A.L. , Novoselova E.S. , Chepanova A.A. , Popova N.A. , Nikolin V.P. , Luzina O.A. , Salakhutdinov N.F. , Ryabchikova E.I. , Lavrik O.I.
Antitumor Activity of the Combination of Topotecan and Tyrosyl-DNA-Phosphodiesterase 1 Inhibitor on Model Krebs-2 Mouse Ascite Carcinoma
Molecular Biology. 2021. V.55. N2. P.273-277. DOI: 10.1134/S0026893321020060 WOS Scopus РИНЦ OpenAlex

Дырхеева Н.С. , Захаренко А.Л. , Новоселова Е.С. , Чепанова А.А. , Попова Н.А. , Николин В.П. , Лузина О.А. , Салахутдинов Н.Ф. , Лаврик О.И.
Противоопухолевая активность комбинации топотекана и ингибитора тирозил-днк-фосфодиэстеразы 1 на модели асцитной карциномы кребс-2 мыши
Молекулярная биология (Molecularnaya biologiya). 2021. Т.55. №2. С.312-317. DOI: 10.31857/S0026898421020051 Scopus РИНЦ OpenAlex

Published print:	Mar 1, 2021
Published online:	Apr 29, 2021

Web of science:	WOS:000646053000011
Scopus:	2-s2.0-85105086411
Elibrary:	46033601
OpenAlex:	W3129279480

DB	Citing
Scopus	4
Web of science	1
Elibrary	6
OpenAlex	7