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Title: Downregulation of oncogenic RAS and c-Myc expression in MOLT-4 leukaemia cells by a salicylaldehyde semicarbazone copper(II) complex
Authors: Goh, Yan Yih
Yan, Yaw Kai
Tan, Nguan Soon
Goh, Su Ann
Li, Shang
Teoh, You Chuan
Lee, Peter Peng Foo
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.
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.
ISSN: 2045-2322 (online)
Other Identifiers: 10.1038/srep36868
Appears in Collections:Journal Articles

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