Open AccessEffect of pivaloyl-substituted pyrrole containing heterocyclic compounds on DNA repair pathways in Ewing sarcoma cells
Author(s) -
Aigul Galembikova,
Галембикова Айгуль Рафиковна,
S V Boychuk,
Бойчук Сергей Васильевич,
Pavel Dunaev,
Дунаев Павел Дмитриевич,
Ramil Khusnutdinov,
Хуснутдинов Рамиль Рамисович,
С. С. Зыкова,
Зыкова Светлана Сергеевна
Publication year - 2018
Publication title -
kazanskij medicinskij žurnal
Language(s) - English
Resource type - Journals
eISSN - 2587-9359
pISSN - 0368-4814
DOI - 10.17816/kmj2018-245
Subject(s) - cell cycle , dna damage , cell cycle checkpoint , dna , apoptosis , checkpoint kinase 2 , chemistry , microbiology and biotechnology , pyrrole , dna repair , chek1 , biology , biochemistry , organic chemistry
Aim. To examine deoxyribonucleic acid (DNA) damage repair and cell cycle regulatory mechanisms of Ewing sarcoma cells exposed to pivaloyl-substituted pyrrole containing heterocyclic compounds.
Methods. The study was performed on A673 Ewing sarcoma cell line. The tumor cells were incubated for 48 h in the presence of pivaloyl-substituted pyrrole containing heterocyclic compounds (compounds №20 and №24). Western blot analysis was utilized to examine expression of the markers of DNA single-strand (phosphorylated forms of ATR and Chk1) and double-strand breaks (phosphorylated forms of H2AX, АТМ, DNA-PK, BRCA-1, Chk-2). Analysis of the cell cycle phases was performed by flow cytometry (BD FacsCanto, USA).
Results. Pivaloyl-substituted pyrrole containing heterocyclic compounds substantially increased the expression of histone 2A phosphorylated on serine 138 (γ-H2AX) that indicates DNA damage (double-strand breaks). Under exposure to pivaloyl-substituted pyrrole containing heterocyclic compounds the studied cells increased expression of phosphorylated forms of ATM-kinase and BRCA-1. Also cell cycle disorders leading to substantial G2/M arrest and enhanced apoptosis of tumor cells were observed.
Conclusion. Pivaloyl-substituted pyrrole containing heterocyclic compounds induced DNA double-strand breaks in A673 Ewing sarcoma cell line; in response to DNA damage in tumor cells, the mechanisms of DNA double-strand breaks repair were activated; despite activation of DNA repair mechanisms, A673 cells underwent cell cycle arrest in the G2/M-phase and apoptosis.