Regulation of Cancer Cell Death by a Novel Compound, C604, in a c-Myc-overexpressing Cellular Environment

Mun Jeong Jo, A Rome Paek, Ji Seung Choi, Chang Youp Ok, Kyung Chae Jeong, Jae Hyang Lim, Seok Hyun Kim, Hye Jin You

Eur J Pharmacol. 2015 Dec 15;769:257-65.

PMID: 26607468

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.

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Catalog Number	Product Name	Structure	CAS Number	Price
AP426834380	NS3694		426834-38-0	Price