DH332, A Synthetic β-carboline Alkaloid, Inhibits B Cell Lymphoma By Activation Of Caspase Family

Objective The purpose of this study was to investigate the anti-tumor effect and safety of DH332, a new β-carboline alkaloids derivatives, in vitro and in vivo.Methods The anti-tumor effects of DH332on human (RAMOS RA.1) and mouse (J558) B lymphoma cell lines were detected using a CCK-8kit (Cell Counting Kit-8), and apoptosis was detected by flow cytometry with PI/AnnexinV staining. Western blotting was used to detected Caspase-3and Caspase-8. Neurotoxic and anti-tumor effect were evaluated in animal experiment, respectively.Results DH332exerts a lower neurotoxicity compared with harmine. It also possesses strong antitumor effects against two B cell lymphoma cell lines with low IC50s. Moreover, DH332could inhibit the proliferation and induce the apoptosis of RAMOS RA.1and J558cell lines in a dose-dependent manner. Our results suggest that DH332triggers apoptosis by mainly activating the caspase signaling pathway. In vivo studies of tumor-bearing BALB/c mice showed that DH332significantly inhibits J558xenograft tumors.Conclusions DH332owns an effective antitumor activity in vitro and in vivo, and has the potential to be a promising drug candidate for lymphoma therapy.