title: 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.
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi, South Korea.
authors.forename: Mun Jeong
authors.initials: MJ
authors.lastname: Jo
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi, South Korea.
authors.forename: A Rome
authors.initials: AR
authors.lastname: Paek
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi, South Korea.
authors.forename: Ji Seung
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi, South Korea.
authors.forename: Chang Youp
authors.initials: CY
authors.lastname: Ok
authors.affiliation: Biomolecular Function Research Branch, Division of Convergence Technology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi, South Korea.
authors.forename: Kyung Chae
authors.initials: KC
authors.lastname: Jeong
authors.affiliation: Department of Microbiology, Ewha Womans University School of Medicine, Seoul, South Korea.
authors.forename: Jae Hyang
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi, South Korea.
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi, South Korea. Electronic address: hjyou@ncc.re.kr.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: You
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C000610700:C604 compound; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D011743:Pyrimidines; D013844:Thiazoles; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3
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)