title: Small molecule selectively suppresses MYC transcription in cancer cells.
abstract: Stauprimide is a staurosporine analog that promotes embryonic stem cell (ESC) differentiation by inhibiting nuclear localization of the MYC transcription factor NME2, which in turn results in down-regulation of MYC transcription. Given the critical role the oncogene MYC plays in tumor initiation and maintenance, we explored the potential of stauprimide as an anticancer agent. Here we report that stauprimide suppresses MYC transcription in cancer cell lines derived from distinct tissues. Using renal cancer cells, we confirmed that stauprimide inhibits NME2 nuclear localization. Gene expression analysis also confirmed the selective down-regulation of MYC target genes by stauprimide. Consistent with this activity, administration of stauprimide inhibited tumor growth in rodent xenograft models. Our study provides a unique strategy for selectively targeting MYC transcription by pharmacological means as a potential treatment for MYC-dependent tumors.
authors.affiliation: California Institute for Biomedical Research, La Jolla, CA 92037.
authors.forename: Claire
authors.initials: C
authors.lastname: Bouvard
authors.affiliation: California Institute for Biomedical Research, La Jolla, CA 92037.
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lim
authors.affiliation: California Institute for Biomedical Research, La Jolla, CA 92037.
authors.forename: John
authors.initials: J
authors.lastname: Ludka
authors.affiliation: California Institute for Biomedical Research, La Jolla, CA 92037.
authors.forename: Nahid
authors.initials: N
authors.lastname: Yazdani
authors.affiliation: California Institute for Biomedical Research, La Jolla, CA 92037.
authors.forename: Ashley K
authors.initials: AK
authors.lastname: Woods
authors.affiliation: California Institute for Biomedical Research, La Jolla, CA 92037.
authors.forename: Arnab K
authors.initials: AK
authors.lastname: Chatterjee
authors.affiliation: California Institute for Biomedical Research, La Jolla, CA 92037 schultz@scripps.edu szhu@calibr.org.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Schultz
authors.affiliation: California Institute for Biomedical Research, La Jolla, CA 92037 schultz@scripps.edu szhu@calibr.org.
authors.forename: Shoutian
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000008:administration & dosage*
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; D016271:Proto-Oncogene Proteins c-myc; D054852:Small Molecule Libraries; C517941:Nme2 protein, mouse
keywords: MYC; NME2; cancer; nuclear localization; stauprimide