title: A Novel Natural Product, KL-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells.
abstract: OBJECTIVE
  The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by Naturin Natural Products, İzmir, Turkey), on 232B4 chronic lymphocytic leukemia (CLL) cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells.
  
  
  METHODS
  The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry.
  
  
  RESULTS
  We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase.
  
  
  CONCLUSIONS
  KL-21 has a growth-inhibitory effect on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1.
authors: Aysun
authors: A
authors: Adan Gökbulut
authors: Mustafa
authors: M
authors: Yaşar
authors: İzmir Institute of Technology Faculty of Science, Department of Molecular Biology and Genetics, İzmir, Turkey Phone: +90 232 750 73 15 E-mail: ybaran@gmail.com.
authors: Yusuf
authors: Y
authors: Baran
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products; D053148:Caspase 3 / Q000032:analysis; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009363:Neoplasm Proteins / Q000032:analysis; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; C000613554:KL-21 plant preparation; D009363:Neoplasm Proteins; D010936:Plant Extracts; C505407:CASP3 protein, human; D053148:Caspase 3