title: Antineoplastic effects of deoxypodophyllotoxin, a potent cytotoxic agent of plant origin, on glioblastoma U-87 MG and SF126 cells.
abstract: BACKGROUND
  Deoxypodophyllotoxin (DPT) is a semi-synthetic compound derived from the extract of Dysosma versipellis (Hance) M. Cheng, one of the most popular Chinese herbal medicines. The present study evaluates the in vitro cytotoxicity of DPT on a wide panel of human cancer cell lines and investigates its molecular mechanism of action on high grade glioma U-87 MG and SF126 cells.
  
  
  METHODS
  The growth inhibitory effect of DPT on different types of human cancer cells was measured by the Cell Counting Kit-8 (CCK-8) assay. For the elucidation of the nature of the cellular response to DPT-treatment; flow cytometry-based assays, light and fluorescent microscopy, caspase colorimetric and inhibition assays, and Western blot analysis were performed.
  
  
  RESULTS
  Our data show that DPT possesses a potent growth-inhibitory action, with IC50 values in nanomolar ranges. Cell cycle analysis revealed G2/M phase arrest in a dose- and time-dependent manner before cell death occurred. Additional studies indicated that DPT induced G2 arrest in U-87 MG cells by decreasing the expression of Cdc2, cyclin B1, and Cdc25C proteins. In contrast, DPT failed to down-regulate these cell cycle regulatory molecules in SF126 glioblastoma cells and stopped the cell cycle at M phase. Interestingly, morphological changes and biochemical markers such as phosphatydylserine externalization, DNA fragmentation, and caspase activation, confirmed that DPT-treatment resulted in an induction of apoptosis in both examined cell lines via caspase-dependent pathways.
  
  
  CONCLUSIONS
  Taken together, our data demonstrated that DPT possesses a potent in vitro cytotoxic activity and exerts its effect via G2/M arrest and apoptosis.
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, China.
authors.forename: Mounia
authors.initials: M
authors.lastname: Guerram
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, China; Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, China. Electronic address: beaglejiang@cpu.edu.cn.
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Jiang
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, China; Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, China; Medical and Chemical Institute, China Pharmaceutical University, Nanjing, China. Electronic address: lyzhang@cpu.edu.cn.
authors.forename: Lu-Yong
authors.initials: LY
authors.lastname: Zhang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000096:biosynthesis; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D020687:cdc25 Phosphatases / Q000096:biosynthesis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D056744:Cyclin B1; D004365:Drugs, Chinese Herbal; C014451:deoxypodophyllotoxin; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D020169:Caspases; D011034:Podophyllotoxin
keywords: Cdc2/Cyclin B1; Deoxypodophyllotoxin; Glioblastoma