Research output: Contribution to journal › Article › peer-review
Effect of Usnic Acid-Derived Tyrosyl-DNA Phosphodiesterase 1 Inhibitor Used as Monotherapy or in Combination with Olaparib on Transplanted Tumors In Vivo. / Kornienko, T. E.; Zakharenko, A. L.; Ilina, E. S. et al.
In: Molecular Biology, Vol. 57, No. 2, 04.2023, p. 214-224.Research output: Contribution to journal › Article › peer-review
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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 -
ID: 59649015