ArticleCell biology and toxicology2023
Exploring the ATR-CHK1 pathway in the response of doxorubicin-induced DNA damages in acute lymphoblastic leukemia cells.
Article in Cell biology and toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- RMI2 knockdown suppresses ovarian cancer cell growth by impairing DNA damage repair via the ATR/CHK1 signaling pathway.In vitro cellular & developmental biology. Animal · 2026Article
- Sublethal DNA damage switches off B cell effector programs in an RA-FLS-PBMC co-culture.Cell death discovery · 2026Article
- Doxorubicin induces ferroptosis in endometrial cancer by suppressing the MKK6/p38/CEBPB axis.Journal of translational medicine · 2026Article
- The CHK1 inhibitor Prexasertib is effective againstFrontiers in endocrinology · 2026Article
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Integrative miRNOMe profiling reveals the miR-195-5p-CHEK1 axis and its impact on luminal breast cancer outcomes.Molecular oncology · 2025Article
- Knockdown of EBP1 promotes doxorubicin-induced apoptosis in renal clear cell carcinoma cells through activation of the p38/HIF-1α pathway.Oncology letters · 2025Article
- Multifaced Anticancer Potential of Doxorubicin: Spotlight on Breast Cancer.Diseases & research · 2025Article
- Flavonoids as Chemosensitizers in Leukemias.Advances in experimental medicine and biology · 2025Review
- Indigofera suffruticosa aerial parts extract induce G2/M arrest and ATR/CHK1 pathway in Jurkat cells.BMC complementary medicine and therapies · 2024Article
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Review
- ATR inhibition sensitizes liposarcoma to doxorubicin by increasing DNA damage.American journal of cancer research · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Doxorubicin (Dox) is one of the most commonly used anthracyclines for the treatment of solid and hematological tumors such as B-/T cell acute lymphoblastic leukemia (ALL). Dox compromises topoisomerase II enzyme functionality, thus inducing structural damages during DNA replication and causes direct damages intercalating into DNA double helix. Eukaryotic cells respond to DNA damages by activating the ATM-CHK2 and/or ATR-CHK1 pathway, whose function is to regulate cell cycle progression, to promote damage repair, and to control apoptosis. We evaluated the efficacy of a new drug schedule combining Dox and specific ATR (VE-821) or CHK1 (prexasertib, PX) inhibitors in the treatment of human B-/T cell precursor ALL cell lines and primary ALL leukemic cells. We found that ALL cell lines respond to Dox activating the G2/M cell cycle checkpoint. Exposure of Dox-pretreated ALL cell lines to VE-821 or PX enhanced Dox cytotoxic effect. This phenomenon was associated with the abrogation of the G2/M cell cycle checkpoint with changes in the expression pCDK1 and cyclin B1, and cell entry in mitosis, followed by the induction of apoptosis. Indeed, the inhibition of the G2/M checkpoint led to a significant increment of normal and aberrant mitotic cells, including those showing tripolar spindles, metaphases with lagging chromosomes, and massive chromosomes fragmentation. In conclusion, we found that the ATR-CHK1 pathway is involved in the response to Dox-induced DNA damages and we demonstrated that our new in vitro drug schedule that combines Dox followed by ATR/CHK1 inhibitors can increase Dox cytotoxicity against ALL cells, while using lower drug doses. • Doxorubicin activates the G2/M cell cycle checkpoint in acute lymphoblastic leukemia (ALL) cells. • ALL cells respond to doxorubicin-induced DNA damages by activating the ATR-CHK1 pathway. • The inhibition of the ATR-CHK1 pathway synergizes with doxorubicin in the induction of cytotoxicity in ALL cells. • The inhibition of ATR-CHK1 pathway induces aberrant chromosome segregation and mitotic spindle defects in doxorubicin-pretreated ALL cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.