title: In vitro induction of apoptotic cell death in chronic lymphocytic leukemia by two natural products: preliminary study.
abstract: OBJECTIVE
  B cell chronic lymphocytic leukemia (B-CLL) is an neoplastic disorder characterized by alterations in the pathways of programmed cell death (apoptosis). Deregulation of apoptosis pathways also contributes to chemoresistance of B-CLL cells. Therefore, it is not surprising that induction and acceleration of apoptosis represent key point in novel B-CLL therapeutic protocols. The present study was designed to investigate the effects of two natural products, Immunarc forte and Korbazol on the in vitro survival of leukemic cells.
  
  
  METHODS
  peripheral blood mononuclear cells (PBMC) from 20 B-CLL patients and 20 healthy donors were used for cytotoxicity studies. Cytotoxic activity of the tested products were assessed by the MTT colorimetric assay and the type of cell death was determined by flow cytometry.
  
  
  RESULTS
  we found that Korbazol was selectively cytotoxic against B-CLL cells, but the cytotoxic activity of Immunarc forte was much weaker. Of note, synergy was shown between these two drugs, and this effect was also selective, without affecting the normal mononuclear cells. According to Annexin-V binding, Korbazol and Immunarc forte induced apoptotic type of cell death in B-CLL cells. Moreover, treatment with Korbazol, but not with Immunarc forte, decreased spontaneous apoptosis in cultured normal polymorphonuclear cells.
  
  
  CONCLUSIONS
  our findings imply that Korbazol is as potential therapeutic agent that induces apoptosis of B-CLL cells. The resistance of normal mononuclear cells and anti-apoptotic effects on normal polymorphonuclear cells, as well as its ability to synergize with Immunarc forte, warrants further investigation and supports their therapeutic application in the treatment of B-CLL.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, University of Kragujevac, Kragujevac, Serbia. dejan.baskic@gmail.com
authors.forename: D
authors.initials: D
authors.lastname: Baskic
authors.forename: N
authors.initials: N
authors.lastname: Ilic
authors.forename: S
authors.initials: S
authors.lastname: Popovic
authors.forename: P
authors.initials: P
authors.lastname: Djurdjevic
authors.forename: P
authors.initials: P
authors.lastname: Ristic
authors.forename: D
authors.initials: D
authors.lastname: Avramovic
authors.forename: N
authors.initials: N
authors.lastname: Arsenijevic
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001688:Biological Products / Q000494:pharmacology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy / Q000473:pathology*
chemical_list: D017304:Annexin A5; D001688:Biological Products