Background: 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 CML. Objectives: To clarify the effects of c-Myc inhibition in CML, we examined the anti-tumor property of a well-known small molecule inhibitor of c-Myc 10058-F4 on K562 cell line. Methods: This experimental study was conducted in K562 cell line for evaluation of cytotoxic activity of 10058-F4 using Trypan blue and MTT assays. Flow cytometry and Quantitative RT-PCR analysis were also conducted to determine its mechanism of action. Additionally, Annexin/PI staining was performed for apoptosis assessment. Results: The results of Trypan blue and MTT assay demonstrated that inhibition of c-Myc, as shown by suppression of c-Myc expression and its associated genes PP2A, CIP2A, and hTERT, could decrease viability and metabolic activity of K562 cells, respectively. Moreover, a robust elevation in cell population in G1-phase coupled with up-regulation of p21 and p27 expression shows that 10058-F4 could hamper cell proliferation, at least partly, through induction of G1 arrest. Accordingly, we found that 10058-F4 induced apoptosis via increasing Bax and Bad; In contrast, no significant alterations were observed NF-KB pathway-targeted anti-apoptotic genes in the mRNA levels. Notably, disruption of the NF-κB pathway with bortezomib as a common proteasome inhibitor sensitized K562 cells to the cytotoxic effect of 10058-F4, substantiating the fact that the NF-κB axis functions probably attenuate the K562 cells sensitivity to c-Myc inhibition. Conclusions: It can be concluded from the results of this study that inhibition of c-Myc induces anti-neoplastic effects on CML-derived K562 cells as well as increases the efficacy of imatinib. For further insight into the safety and effectiveness of 10058-F4 in CML, in vivo studies will be required.
Zehtabcheh, S., Sheikh‐Zeineddini, N., Yousefi, A., & Bashash, D. (2024). Anti-Leukemic Effects of Small Molecule Inhibitor of c-Myc (10058-F4) on Chronic Myeloid Leukemia Cells. Asian Pacific Journal of Cancer Prevention, 25(6), 1959-1967. doi: 10.31557/APJCP.2024.25.6.1959
MLA
Sara Zehtabcheh; Negar Sheikh‐Zeineddini; Amir-Mohammad Yousefi; Davood Bashash. "Anti-Leukemic Effects of Small Molecule Inhibitor of c-Myc (10058-F4) on Chronic Myeloid Leukemia Cells". Asian Pacific Journal of Cancer Prevention, 25, 6, 2024, 1959-1967. doi: 10.31557/APJCP.2024.25.6.1959
HARVARD
Zehtabcheh, S., Sheikh‐Zeineddini, N., Yousefi, A., Bashash, D. (2024). 'Anti-Leukemic Effects of Small Molecule Inhibitor of c-Myc (10058-F4) on Chronic Myeloid Leukemia Cells', Asian Pacific Journal of Cancer Prevention, 25(6), pp. 1959-1967. doi: 10.31557/APJCP.2024.25.6.1959
VANCOUVER
Zehtabcheh, S., Sheikh‐Zeineddini, N., Yousefi, A., Bashash, D. Anti-Leukemic Effects of Small Molecule Inhibitor of c-Myc (10058-F4) on Chronic Myeloid Leukemia Cells. Asian Pacific Journal of Cancer Prevention, 2024; 25(6): 1959-1967. doi: 10.31557/APJCP.2024.25.6.1959
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