Regulation of cancer cell death by a novel compound, C604, in a c-Myc-overexpressing cellular environment

Abstract

The proto-oncogene c-Myc has been implicated in a variety of cellular processes, such as proliferation, differentiation and apoptosis. Several c-Myc targets have been studied; however, selective regulation of c-Myc is not easy in cancer cells. Herein, we attempt to identify chemical compounds that induce cell death in c-Myc-overexpressing cells (STF-cMyc and STF-Control) by conducting MTS assays on approximately 4000 chemical compounds. One compound, C604, induced cell death in STF-cMyc cells but not STF-Control cells. Apoptotic proteins, including caspase-3 and poly(ADP-ribose) polymerase (PARP), were cleaved in C604-treated STF-cMyc cells. In addition, SW620, HCT116 and NCI-H23 cells, which exhibit higher basal levels of c-Myc, underwent apoptotic cell death in response to C604, suggesting a role for C604 as an inducer of apoptosis in cancer cells with c-Myc amplification. C604 induced cell cycle arrest at the G2/M phase in cells, which was not affected by apoptotic inhibitors. Interestingly, C604 induced accumulation of c-Myc and Cdc25A proteins. In summary, a chemical compound was identified that may induce cell death in cancer cells with c-Myc amplification specifically through an apoptotic pathway.

Keywords: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (Pubchem CID: 64965); Apoptosis; Bax inhibitor peptide V5 (Pubchem CID: 85854989); Cancer; Caspase-3; Dithiothreitol (Pubchem CID: 446094).; Ethanol (Pubchem CID: 702); Formaldehyde (Pubchem CID: 712); Hoechst 33342 (Pubchem CID: 1464); NS3694 (Pubchem CID: 10109069); NSCI (Pubchem CID: 11591540); c-Myc; dimethylsulfoxide (Pubchem CID: 679); propidium iodide (Pubchem CID: 104981); water-soluble tetrasolium salt WST-8 (Pubchem CID: 9894947).