TY - JOUR
T1 - Regulation of cancer cell death by a novel compound, C604, in a c-Myc-overexpressing cellular environment
AU - Jo, Mun Jeong
AU - Paek, A. Rome
AU - Choi, Ji Seung
AU - Ok, Chang Youp
AU - Jeong, Kyung Chae
AU - Lim, Jae Hyang
AU - Kim, Seok Hyun
AU - You, Hye Jin
N1 - 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.
PY - 2015/12/15
Y1 - 2015/12/15
N2 - 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.
AB - 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.
KW - Apoptosis
KW - c-Myc
KW - Cancer
KW - Caspase-3
UR - http://www.scopus.com/inward/record.url?scp=84948959724&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2015.11.027
DO - 10.1016/j.ejphar.2015.11.027
M3 - Article
C2 - 26607468
AN - SCOPUS:84948959724
SN - 0014-2999
VL - 769
SP - 257
EP - 265
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -