Myc overexpression enhances apoptosis induced by small molecules.
The Myc oncogene is deregulated in a wide variety of human tumors hence the Myc pathway is an attractive target for tailored cancer treatment. We have recently identified two small molecules, MYRAs (Myc-pathway response agents), that induce apoptosis in a Myc-dependent manner and inhibit Myc-driven transformation. Here, we show that these compounds in addition have prominent effects in MYCN overexpressing neuroblastoma cells. A third compound, NSC308848, also induced apoptosis in Myc-overexpressing cells and inhibited Myc-induced cellular transformation. However, in contrast to the MYRAs, NSC308848 treatment resulted in decreased Myc protein levels and gave rise to inhibitory effects also on other transcription factors than Myc. Taken together, our findings suggest that these three small molecules can elicit a similar biological response by interfering with the Myc pathway at different levels.
Mo
Hao
H
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Vita
Marina
M
Crespin
Marianne
M
Henriksson
Marie
M
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D003959:Diamines / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011687:Purines / Q000494:pharmacology
D000873:Anthracenes; D003959:Diamines; D006835:Hydrazones; C511161:NSC 339585; C511162:NSC 45641; D016271:Proto-Oncogene Proteins c-myc; D011687:Purines