Transcription profiling of human multiple myeloma cells treated in vitro with Zalypsis: A novel marine-derived compound with potent antimyeloma activity

ABSTRACT: Multiple Myeloma (MM) remains incurable, and new drugs with novel mechanisms of action are still needed. In this report, we have analyzed the action of Zalypsis, an alkaloid analogous to certain natural marine compounds, in MM. Zalypsis turned out to be the most potent antimyeloma agent we have tested so far, with IC50s from picomolar to low nanomolar ranges. It also showed remarkable ex vivo potency in plasma cells from patients and in MM cells in vivo xenografted in mice. Besides the induction of apoptosis and cell cycle arrest, Zalypsis provoked DNA double-strand-breaks (DSB), evidenced by an increase in phospho-Histone-H2AX and phospho-CHK2, followed by a striking overexpression of p53 in p53-wild type cell lines. In addition, in those cell lines in which p53 was mutated, Zalypsis also

ORGANISM(S): Homo sapiens

SUBMITTER: Enrique Ocio 

PROVIDER: E-GEOD-13662 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress