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

Abstract

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.

Thymoquinone Inhibits JAK/STAT and PI3K/Akt/ mTOR Signaling Pathways in MV4-11 and K562 Myeloid Leukemia Cells

“…Moreover, TQ inhibited the phosphorylation of PI3K and Akt in oral squamous cell carcinoma (KB) cells [38]. Another study has demonstrated that the PTEN protein level was increased, and the PI3K protein level and the phosphorylation of its downstream molecules; Akt and mTOR, were decreased in K562 cells after treatment with ND-09 inhibitory compound [39].…”

miR‑let‑7c‑3p targeting on Egr‑1 contributes to the committed differentiation of leukemia cells into monocyte/macrophages

“…Myeloid leukemia is a type of hematopoietic stem cell malignant tumor with the characteristics of differentiation disorder and uncontrolled proliferation (1,2). At present, the treatment of leukemia is mainly based on the combination of chemotherapy and targeted therapy, but there are obvious side effects and a high recurrence rate.…”

“…Myeloid leukemia is a type of hematopoietic stem cell malignant tumor, with differentiation disorder, uncontrolled proliferation, or the inability of terminal differentiation of primitive cells to retain malignant proliferation ability and accounting for ~15% of new cases of adult leukemia (1,2). It has been confirmed that the occurrence of myeloid leukemia is associated with certain gene mutations, abnormal gene expression, epigenetic disorders or abnormal expression of non-coding RNA (3)(4)(5)(6).…”