title: Plumbagin shows anticancer activity in human osteosarcoma (MG-63) cells via the inhibition of S-Phase checkpoints and down-regulation of c-myc.
abstract: OBJECTIVE
  Plumbagin, a naphthoquinone constituent of Plumbago zeylanica L. (Plumbaginaceae), has been extensively studied for its pharmacological activities and reported to show a good anti-cancer activity in different human cancer cell lines. It is known to exhibit proapoptotic, antiangiogenic and antimetastatic effects in cancer cells. Plumbagin is also known to inhibit NF-κB, JNK (Hsu), PKCε, and STAT-3. However, the anti-proliferatory activity and their core molecular mechanisms have been poorly determined.
  
  
  METHODS
  Human osteosarcoma (MG-63) cells were exposed to plumbagin and the anti-proliferative activity was evaluated by MTT assay. The mechanism of action for the growth inhibitory activity of plumbagin on MG-63 cells was evaluated using flow cytometry for cell cycle distribution, and western blot for assessment of accumulation and phosphorylation of potential target proteins. Furthermore, morphology of MG-63 cells was assessed after treatment with Plumbagin.
  
  
  RESULTS
  Plumbagin has significantly induced growth inhibition against osteosarcoma MG-63 cells, primarily by S-phase cell cycle arrest which is confirmed by the down regulation of cyclin A and CDK2 protein levels determined by western blot analysis. It was also found that plumbagin has triggered the DNA damage in MG-63 cells, subsequently initiating the arrest in S-phase, which is evident by the up-regulation of phosphorylated p53 and histone. Furthermore, plumbagin resulted in the down-regulation of c-myc protein expression in the MG-63 cells.
  
  
  CONCLUSIONS
  Plumbagin has triggered DNA damage and had induced S-phase arrest in MG-63 cells, suggesting it to be a potential compound in treatment against malignant human osteosarcoma.
authors.affiliation: Department of Orthopedics, Jiujiang No. 1 People's Hospital Jiujiang 332000, China.
authors.forename: Chao-Hua
authors.initials: CH
authors.lastname: Yan
authors.affiliation: Department of Orthopedics, Jiujiang No. 1 People's Hospital Jiujiang 332000, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Guangdong Academy of Medical Science Guangzhou 510080, China ; Department of Orthopedics, Guangdong General Hospital Guangzhou 510080, China.
authors.forename: Yuan-Chen
authors.initials: YC
authors.lastname: Ma
keywords: CDK2; Osteosarcoma; cyclin A; p53; phosphorylation; plumbagin