期刊
ANTICANCER RESEARCH
卷 43, 期 7, 页码 3023-3028出版社
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.16473
关键词
MYC; leukaemia; MYC inhibitor; MYC-MAX complex
类别
In this study, the effects of MYC inhibitors on acute leukaemia cell lines were examined. It was found that these inhibitors suppressed cell growth and regulated the expression of various signaling proteins and transcription factors. They also showed potential in targeting NOTCH1-mutated T-ALL.
Background/Aim: MYC proto-oncogene bHLH transcription factor (MYC) proteins function as transcription factors by binding to MYC- associated factor X (MAX) proteins and are involved in various cancer growth, including leukaemia. This study aimed to examine the effects of synthetic MYC inhibitors, which block the MYC- MAX complex formation, in in vitro human acute leukaemia cell lines. Materials and Methods: Four cell lines, OCI/AML2 derived from acute myeloid leukaemia, NALM-6 from B-lymphoblastic leukaemia, and KOPT-K1 and Jurkat from notch receptor 1 (NOTCH1)-mutated T-lymphoblastic leukaemia (T-ALL), were treated with the small-molecule MYC inhibitors 10058-F4 and MYCi975. The expression of cell proliferation and signalling proteins was studied. Results: These inhibitors suppressed the growth of leukaemia cell lines. Treatment with the two inhibitors down- regulated the protein expression of c-MYC, MAX, and activating enhancer-binding protein 4 (AP4) in all cell lines. Up-regulation of p27 and p21 was observed only in 10058-F4-treated OCI/ AML2 cells and MYCi975-treated KOPT-K1 cells. These two inhibitors down-regulated the expression of NOTCH1, cleaved NOTCH1, and hes family bHLH transcription factor 1 (HES1) in both T-ALL cell lines. Conclusion: MYC inhibitors appear to be novel molecular-targeted drugs against acute leukaemia, including NOTCH1-mutated T-ALL. However, it is necessary to elucidate the precise molecular mechanisms of these effects before clinical use.
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