DH332, a Synthetic β-Carboline Alkaloid, Inhibits B Cell Lymphoma Growth by Activation of the Caspase Family


Aim: The purpose of this study was to investigate anti-tumor effects and safety of DH332, a new β-carbolinealkaloids 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 apoptosiswas detected by flow cytometry with PI/annexinV staining. Western blotting was used to detected caspase-3 andcaspase-8. Neurotoxic and anti-tumor effects were evaluated in animal experiments.
Results: DH332 exerts a lowerneurotoxicity compared with harmine. It also possesses strong antitumor effects against two B cell lymphomacell lines with low IC50s. Moreover, DH332 could inhibit the proliferation and induce the apoptosis of RAMOSRA.1 and J558 cell lines in a dose-dependent manner. Our results suggest that DH332 triggers apoptosis bymainly activating the caspase signaling pathway. In vivo studies of tumor-bearing BALB/c mice showed thatDH332 significantly inhibited growth of J558 xenograft tumors.
Conclusions: DH332 exerts effective antitumoractivity in vitro and in vivo, and has the potential to be a promising drug candidate for lymphoma therapy.