The alkaloid emetine as a promising agent for the induction and enhancement of drug-induced apoptosis in leukemia cells.
Emetine, a natural alkaloid from Psychotria ipecacuanha, has been used in phytomedicine to induce vomiting, and to treat cough and severe amoebiasis. Certain data suggest the induction of apoptosis by emetine in leukemia cells. Therefore, we examined the suitability of emetine for the sensitisation of leukemia cells to apoptosis induced by cisplatin. In response to emetine, we found a strong reduction in viability, an induction of apoptosis and caspase activity comparable to the cytotoxic effect of cisplatin. Moreover, emetine had an additive effect and increased cisplatin-induced apoptosis. Mechanistically, we demonstrate by DNA array analysis that emetine alone or together with cisplatin down-regulates several anti-survival genes and up-regulates several pro-apoptotic signalling molecules along with other effects on signalling. These data show that emetine is a strong inducer of apoptosis in leukemia cells and could be a suitable cytotoxic drug alone or in combination with other chemotherapeutics to sensitise leukemia cells to apoptosis.
Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Germany.
Maren
M
Möller
Kerstin
K
Herzer
Till
T
Wenger
Ingrid
I
Herr
Michael
M
Wink
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D017931:DNA Primers; D004640:Emetine / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D009693:Nucleic Acid Hybridization; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification
D017931:DNA Primers; D011500:Protein Synthesis Inhibitors; D012334:RNA, Neoplasm; D020169:Caspases; D004640:Emetine