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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)257-265
Number of pages9
JournalEuropean Journal of Pharmacology
Volume769
DOIs
StatePublished - 15 Dec 2015

Bibliographical note

Funding Information:
This work was supported in part by National Cancer Center, South Korea Grant 1110022 (to H.J. You) and 1410120 (to H.J. You) and National Research Foundation of Korea (NRF) Grant funded by the Korea government ( MSIP, South Korea ) (No. 2015R1A2A2A01003829 ).

Publisher Copyright:
© 2015 Elsevier B.V.

Keywords

  • Apoptosis
  • c-Myc
  • Cancer
  • Caspase-3

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