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Asian Pac J Cancer Prev ; 15(9): 3901-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24935571

RESUMO

AIM: The purpose of this study was to investigate anti-tumor effects and safety of DH332, a new ß-carboline alkaloids derivatives in vitro and in vivo. MATERIALS AND METHODS: The effects of DH332 on human (RAMOS RA.1) and mouse (J558) B lymphoma cell lines were detected using a CCK-8 kit (Cell Counting Kit-8), and apoptosis was detected by flow cytometry with PI/annexinV staining. Western blotting was used to detected caspase-3 and caspase-8. Neurotoxic and anti-tumor effects were evaluated in animal experiments. RESULTS: DH332 exerts a lower neurotoxicity compared with harmine. It also possesses strong antitumor effects against two B cell lymphoma cell lines with low IC50s. Moreover, DH332 could inhibit the proliferation and induce the apoptosis of RAMOS RA.1 and J558 cell lines in a dose-dependent manner. Our results suggest that DH332 triggers apoptosis by mainly activating the caspase signaling pathway. In vivo studies of tumor-bearing BALB/c mice showed that DH332 significantly inhibited growth of J558 xenograft tumors. CONCLUSIONS: DH332 exerts effective antitumor activity in vitro and in vivo, and has the potential to be a promising drug candidate for lymphoma therapy.


Assuntos
Carbolinas/farmacologia , Caspase 3/metabolismo , Caspase 8/metabolismo , Linfoma de Células B/tratamento farmacológico , Alcaloides/efeitos adversos , Alcaloides/farmacologia , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carbolinas/efeitos adversos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Harmina/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
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