ND‑09 inhibits chronic myeloid leukemia K562 cell growth by regulating BCR‑ABL signaling

• Published in: Oncology reports Vol. 46; no. 1; p. 1
• Main Authors: Liu, Yan-Hong, Zhu, Man, Lei, Pan-Pan, Pan, Xiao-Yan, Ma, Wei-Na
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.07.2021; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Analysis; Antibodies; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Benzamides - chemistry; Benzamides - pharmacology; Biotechnology; Bone marrow; Cell culture; Cell cycle; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chromosomes; Chronic myeloid leukemia; Down-Regulation; Drug resistance; Fusion Proteins, bcr-abl - genetics; Fusion Proteins, bcr-abl - metabolism; Gene Expression Regulation, Neoplastic - drug effects; Growth; Humans; Jurkat Cells; K562 Cells; Kinases; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Nilotinib; Penicillin; Phosphorylation; Proteins; Reagents; Real time; Signal Transduction - drug effects; Software; Stem cells; China; cell apoptosis; chronic myeloid leukemia; BCR‑ABL; cell cycle; ND‑09
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2021.8087

Chronic myeloid leukemia (CML) accounts for approximately 15% of new adult leukemia cases. The fusion gene is an important biological basis and target for CML. In the present study, a novel compound, ND‑09, was developed and its inhibitory effect and mechanism of action on CML growth were evaluated using RT‑PCR and western blot analysis. The results showed that ND‑09 demonstrated a high level of inhibitory action toward CML cells overexpressing BCR‑ABL and induced K562 cell apoptosis through the mitochondrial pathway. Notably, combined ND‑09 and siRNA treatment could better inhibit cell proliferation and induce apoptosis in K562 cells. Furthermore, this growth effect of siRNA could be fully rescued by transfection with . ND‑09 exhibited a good fit within BCR‑ABL and occupied its ATP‑binding pocket, thus altering BCR‑ABL kinase activity. Therefore, ND‑09 downregulated the phosphorylation of BCR‑ABL and ABL, ultimately inhibiting the downstream signaling pathways in K562 cells. These findings suggest that ND‑09 induces growth arrest in CML cells by targeting BCR‑ABL.