Please use this identifier to cite or link to this item: http://hdl.handle.net/10497/18263
Title: 
Downregulation of oncogenic RAS and c-Myc expression in MOLT-4 leukaemia cells by a salicylaldehyde semicarbazone copper(II) complex
Authors: 
Issue Date: 
2016
Publisher: 
Nature Publishing Group
Citation: 
Goh, Y.-Y., Yan, Y.-K., Tan, N. S., Goh, S.-A, Li, S., Teoh, Y.-C., & Lee, P. P. F. (2016). Downregulation of oncogenic RAS and c-Myc expression in MOLT-4 leukaemia cells by a salicylaldehyde semicarbazone copper(II) complex. Scientific Reports, 6: 36868. http://dx.doi.org/10.1038/srep36868
Abstract: 
Copper complexes with potent anti-tumor effect have been extensively developed. Most investigations
of their modes of action focused on the biomolecular targets but not the signal transduction between
target binding and cell death. We have previously shown that the cytotoxic complex pyridine(2,4-
dihydroxybenzaldehyde dibenzyl semicarbazone)copper(II) (complex 1) shows selective binding to
human telomeric G-quadruplex DNA over double-stranded DNA in vitro. Herein, we elucidate the
mechanism of action by which complex 1 induces apoptosis in MOLT-4 cells. Complex 1 accumulates
in the nuclei and differentially downregulates the expression of c-Myc, c-Kit and KRAS oncogenes.
Chemical affinity capture assay results show that the complex is associated with c-Myc and KRAS
quadruplex sequences in MOLT-4 cells. We further showed that the reduction in Ras protein expression
resulted in attenuated MEK-ERK and PI3K-Akt signalling activities, leading to the activation of caspasedependent
apoptosis. Notably, complex 1 increased the sensitivity of MOLT-4 cells to cisplatin and vice
versa. Overall, we demonstrated that complex 1 induces apoptosis, at least in part, by suppressing
KRAS, c-Kit and c-Myc oncogene expression and the pro-survival MEK-ERK and PI3K-Akt signalling
pathways.
URI: 
ISSN: 
2045-2322 (online)
Other Identifiers: 
10.1038/srep36868
Website: 
Appears in Collections:Journal Articles

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