TY - JOUR

T1 - Effect of Usnic Acid-Derived Tyrosyl-DNA Phosphodiesterase 1 Inhibitor Used as Monotherapy or in Combination with Olaparib on Transplanted Tumors In Vivo

AU - Kornienko, T. E.

AU - Zakharenko, A. L.

AU - Ilina, E. S.

AU - Chepanova, A. A.

AU - Zakharova, O. D.

AU - Dyrkheeva, N. S.

AU - Popova, N. A.

AU - Nikolin, V. P.

AU - Filimonov, A. S.

AU - Luzina, O. A.

AU - Salakhutdinov, N. F.

AU - Lavrik, O. I.

N1 - This work was supported by the Russian Science Foundation (project no. 21-14-00105; Т.Е. Kornienko, N.S. Dyrkheeva, А.L. Zakharenko, А.S. Filimonov, А.А. Chepanova, N.А. Popova, and V.P. Nikolin) and a state contract with the Institute of Chemical Biology and Fundamental Medicine (project no. 121031300041-4; Е.S. Ilina, О.D. Zakharova, and О.I. Lavrik). Публикация для корректировки.

PY - 2023/4

Y1 - 2023/4

N2 - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that removes various adducts from the 3' end of DNA. Such adducts are formed by enzymes that introduce single-strand breaks in DNA during catalysis (for example, topoisomerase 1) and a number of anticancer drugs with different mechanisms of action. Poly(ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes posttranslational modification (PARylation) of various targets and thus controls many cell processes, including DNA repair. Tdp1 is a PARP1 target, and its PARylation attracts Tdp1 to the site of DNA damage. Olaparib is a PARP1 inhibitor used in clinical practice to treat homologous recombination-deficient tumors. Olaparib inhibits PARylation and, therefore, DNA repair. The Tdp1 inhibitor OL7-43 was used in combination with olaparib to increase the antitumor effect of the latter. Olaparib cytotoxicity was found to increase in the presence of OL7-43 in vitro. OL7-43 did not exert a sensitizing effect, but showed its own antitumor and antimetastatic effects in Lewis and Krebs-2 carcinoma models.

AB - Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that removes various adducts from the 3' end of DNA. Such adducts are formed by enzymes that introduce single-strand breaks in DNA during catalysis (for example, topoisomerase 1) and a number of anticancer drugs with different mechanisms of action. Poly(ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes posttranslational modification (PARylation) of various targets and thus controls many cell processes, including DNA repair. Tdp1 is a PARP1 target, and its PARylation attracts Tdp1 to the site of DNA damage. Olaparib is a PARP1 inhibitor used in clinical practice to treat homologous recombination-deficient tumors. Olaparib inhibits PARylation and, therefore, DNA repair. The Tdp1 inhibitor OL7-43 was used in combination with olaparib to increase the antitumor effect of the latter. Olaparib cytotoxicity was found to increase in the presence of OL7-43 in vitro. OL7-43 did not exert a sensitizing effect, but showed its own antitumor and antimetastatic effects in Lewis and Krebs-2 carcinoma models.

KW - Krebs-2 carcinoma

KW - Lewis carcinoma

KW - Tdp1 inhibitor

KW - olaparib

KW - tyrosyl-DNA phosphodiesterase 1

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85156165338&origin=inward&txGid=590a63e00e2c0c10d71a705146721f26

UR - https://www.mendeley.com/catalogue/c2cdd9cc-764c-3753-846b-f33d095154e3/

U2 - 10.1134/S0026893323020127

DO - 10.1134/S0026893323020127

M3 - Article

VL - 57

SP - 214

EP - 224

JO - Molecular Biology

JF - Molecular Biology

SN - 0026-8933

IS - 2

ER -