Details

Autor(en) / Beteiligte

• Kornienko, T E
• Zakharenko, A L
• Ilina, E S
• Chepanova, A A
• Zakharova, O D
• Dyrkheeva, N S
• Popova, N A
• Nikolin, V P
• Filimonov, A S
• Luzina, O A
• Salakhutdinov, N F
• Lavrik, O I

Titel

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

Ist Teil von

• Molekuliarnaia biologiia, 2023-03, Vol.57 (2), p.220

Ort / Verlag

Russia (Federation)

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.