title: DH332, a synthetic β-carboline alkaloid, inhibits B cell lymphoma growth by activation of the caspase family.
abstract: OBJECTIVE
  The purpose of this study was to investigate anti-tumor effects and safety of DH332, a new β-carboline alkaloids derivatives in vitro and in vivo.
  
  
  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.
authors.affiliation: Research Center for Immunology, Xinxiang Medical University, East of JinSui Road of XinXiang City, Xinxiang, China E-mail : zhihai@ibp.ac.cn, wanghui@xxmu.edu.cn.
authors.forename: Pan
authors.initials: P
authors.lastname: Gao
authors.forename: Ning
authors.initials: N
authors.lastname: Tao
authors.forename: Qin
authors.initials: Q
authors.lastname: Ma
authors.forename: Wen-Xi
authors.initials: WX
authors.lastname: Fan
authors.forename: Chen
authors.initials: C
authors.lastname: Ni
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Zhi-Hai
authors.initials: ZH
authors.lastname: Qin
mesh_terms: D000470:Alkaloids / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002243:Carbolines / Q000009:adverse effects / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D006247:Harmine / Q000494:pharmacology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D002243:Carbolines; C000597038:DH332; D006247:Harmine; D053148:Caspase 3; D053181:Caspase 8