Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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DH332, a Synthetic β-Carboline Alkaloid, Inhibits B Cell Lymphoma Growth by Activation of the Caspase Family

  • Gao, Pan (Research Center for Immunology, Xinxiang Medical University, East of JinSui Road of XinXiang City) ;
  • Tao, Ning (Protein & Peptide Pharmaceutical Laboratory, Institute of Biophysics, Chinese Academy of Sciences) ;
  • Ma, Qin (Xinjiang Huashidan Pharmaceutical Co. Ltd.) ;
  • Fan, Wen-Xi (Xinjiang Huashidan Pharmaceutical Co. Ltd.) ;
  • Ni, Chen (Protein & Peptide Pharmaceutical Laboratory, Institute of Biophysics, Chinese Academy of Sciences) ;
  • Wang, Hui (Research Center for Immunology, Xinxiang Medical University, East of JinSui Road of XinXiang City) ;
  • Qin, Zhi-Hai (Protein & Peptide Pharmaceutical Laboratory, Institute of Biophysics, Chinese Academy of Sciences)
  • Published : 2014.05.15
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Abstract

Aim: The purpose of this study was to investigate anti-tumor effects and safety of DH332, a new ${\beta}$-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 $IC_{50s}$. 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.

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References

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