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

Chronic myeloid leukemia (CML) accounts for approximately 15% of new adult leukemia cases. The fusion gene BCR-ABL 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 BCR-ABL siRNA treatment could better inhibit cell proliferation and induce apoptosis in K562 cells. Furthermore, this growth effect of BCR-ABL siRNA could be fully rescued by transfection with BCR-ABL. 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.

Automated summary

The study revealed that the novel compound ND-09 inhibited CML cell growth by targeting BCR-ABL and altering its kinase activity, ultimately leading to growth arrest in CML cells.