KEY TAKEAWAYS
- The study aimed to investigate the anti-tumor effects of c-Myc inhibition using the small molecule inhibitor 10058-F4 in the K562 cell line of CML.
- Inhibition of c-Myc with 10058-F4 enhances anti-CML effects and synergizes with imatinib, suggesting promise for clinical development.
As one of the main molecules in BCR-ABL signaling, c-Myc acts as a pivotal key in disease progression and disruption of long-term remission in patients with Chronic Myeloid Leukemia (CML).
To clarify the effects of c-Myc inhibition in CML, Sara Zehtabcheh and the team aimed to examine the anti-tumor property of a well-known small molecule inhibitor of c-Myc, 10058-F4, on the K562 cell line.
They performed an inclusive analysis in the K562 cell line to evaluate the cytotoxic activity of 10058-F4 using Trypan blue and MTT assays. Flow cytometry and Quantitative RT-PCR analysis were conducted to determine its mechanism of action. Additionally, Annexin/PI staining was performed for apoptosis assessment.
They found that inhibition of c-Myc, as shown by suppression of c-Myc expression and its associated genes PP2A, CIP2A, and hTERT, decreased viability and metabolic activity of K562 cells. A robust elevation in cell population in G1-phase, coupled with up-regulation of p21 and p27 expression, indicated that 10058-F4 could hamper cell proliferation through induction of G1 arrest.
Additionally, 10058-F4 induced apoptosis via increasing Bax and Bad; however, no significant alterations were observed in NF-κB pathway-targeted anti-apoptotic genes at the mRNA level. Disruption of the NF-κB pathway with bortezomib sensitized K562 cells to the cytotoxic effect of 10058-F4, suggesting that NF-κB axis functions may attenuate K562 cells’ sensitivity to c-Myc inhibition.
The study concluded that inhibition of c-Myc induces anti-neoplastic effects on CML-derived K562 cells and enhances the efficacy of imatinib. Further insights into the safety and effectiveness of 10058-F4 in CML will necessitate in vivo studies.
No funding-related information was given.
Source: https://pubmed.ncbi.nlm.nih.gov/38918657/
Zehtabcheh S, Sheikh-Zeineddini N, Yousefi AM, et al. (2024). “Anti-Leukemic Effects of Small Molecule Inhibitor of c-Myc (10058-F4) on Chronic Myeloid Leukemia Cells.” Asian Pac J Cancer Prev. 2024 Jun 1;25(6):1959-1967. doi: 10.31557/APJCP.2024.25.6.1959. PMID: 38918657.
