title: Oleanolic acid isolated from ethanolic extract of Phytolacca decandra induces apoptosis in A375 skin melanoma cells: drug-DNA interaction and signaling cascade.
abstract: OBJECTIVE
  Oleanolic acid (OA) has been reported to have anticancer effects, but the extent of its cytotoxicity, its ability to interact with nuclear DNA, its action against skin melanoma, as well as the molecular mechanism of its action against cell proliferation and in support of cell death are still unexplored. This led us to examine the efficacy of OA, a bioactive compound isolated from Phytolacca decandra, on these issues in the present investigation.
  
  
  METHODS
  Studies related to analyses of cell viability, drug-DNA interaction, cell proliferation, cell cycle and epidermal growth factor receptor (EGFR) activity were performed. To investigate whether cells undergo apoptosis, studies like fluorescence microscopy, poly (ADP-ribose) polymerase (PARP) degradation, annexin V-fluorescein isothiocyanate/propidium iodide assay, alteration in mitochondrial membrane potential and activity of some relevant signaling proteins were performed.
  
  
  RESULTS
  OA displayed a minimal and negligible cytotoxic effect on normal HaCaT cells (skin keratinocytes) and peripheral blood mononuclear cells but by contrast it reduced A375 cell viability significantly. OA interacted with nuclear DNA quickly after exposure. It acted as an anti-proliferative agent. It suppressed EGFR activity. OA administration led the cells to mitochondria-dependent caspase 3-mediated apoptosis.
  
  
  CONCLUSIONS
  OA interacts with cellular DNA, inhibits proliferation possibly through modulating EGFR activity and induces mitochondria-dependent caspase 3-mediated apoptosis in A375 cells which would qualify it as a potent anticancer agent.
authors.affiliation: Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani-741235, West Bengal, India.
authors.forename: Samrat
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani-741235, West Bengal, India.
authors.forename: Kausik
authors.initials: K
authors.lastname: Bishayee
authors.affiliation: Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani-741235, West Bengal, India; E-mail: prof_arkb@yahoo.co.in; khudabukhsh_48@rediffmail.com.
authors.forename: Anisur Rahman
authors.initials: AR
authors.lastname: Khuda-Bukhsh
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000187:drug effects*; D066246:ErbB Receptors / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*; D008856:Microscopy, Fluorescence; D009828:Oleanolic Acid / Q000302:isolation & purification / Q000627:therapeutic use*; D029603:Phytolacca / Q000737:chemistry*; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D010936:Plant Extracts; D009828:Oleanolic Acid; C512478:EGFR protein, human; D066246:ErbB Receptors