RESUMO
BACKGROUND: It was recently confirmed that the antifungal agent ciclopirox olamine inhibits Wnt/beta catenin signaling in myeloma. Piroctone olamine (PO) has very similar chemical features to ciclopirox olamine. MATERIALS AND METHODS: This study investigated the antitumor effect of PO in vitro and in vivo in a murine myeloma model. RESULTS: PO demonstrated a major apoptotic activity in various human and murine myeloma and lymphoma cell lines, as well as in human primary cells. In vivo, tumor growth, as well as overall survival, was significantly reduced in mice treated with PO as compared to untreated mice. Interestingly, concerning tumor growth and survival of the animals, a significant additive effect was seen by the combination of lenalidomide plus PO as compared to single application. CONCLUSION: These results reveal a significant selective induction of apoptosis by PO and suggest a significant in vivo effect against myeloma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Etanolaminas/uso terapêutico , Linfoma/tratamento farmacológico , Mieloma Múltiplo/tratamento farmacológico , Piridonas/uso terapêutico , Talidomida/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Combinação de Medicamentos , Humanos , Lenalidomida , Camundongos , Camundongos Endogâmicos BALB C , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
We recently confirmed that ciclopirox olamine inhibits Wnt/beta catenin signalling in myeloma. Griseofulvin (GF) has similar chemical features as compared to ciclopirox olamine. In this study the anti-tumor effect of GF was investigated. GF demonstrated a major apoptotic activity in various human and murine myeloma and lymphoma cell lines as well as in human primary cells. In vivo, tumor growth as well as overall survival were significantly reduced in mice treated with GF as compared to untreated mice. In conclusion, our results reveal a significant selective induction of apoptosis by GF and suggest a significant in vivo effect against myeloma.
