RT Journal Article
SR Electronic
T1 Effects of MYC Inhibitors on the Growth of Acute Leukaemia Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3023
OP 3028
DO 10.21873/anticanres.16473
VO 43
IS 7
A1 NOGUCHI, KOTOMI
A1 ITOH, MAI
A1 ITO, CHISUZU
A1 TOHDA, SHUJI
YR 2023
UL http://ar.iiarjournals.org/content/43/7/3023.abstract
AB 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.