title: Bryonia dioica aqueous extract induces apoptosis through mitochondrial intrinsic pathway in BL41 Burkitt's lymphoma cells.
abstract: BACKGROUND
  Bryonia dioica Jacq. is a climbing perennial herb with tuberous roots which is widely used in traditional medicine in Algeria for the treatment of cancers; it belongs to the genus Bryonia (Cucurbitaceae).
  
  
  OBJECTIVE
  To investigate the cytotoxic and apoptogenic activities, the phytochemical composition and acute toxicity of the aqueous extract of Bryonia dioica roots growing in Algeria.
  
  
  METHODS
  Dried roots of Bryonia dioica were extracted with water (decoction). The cytotoxic effects of the aqueous extract in the Burkitt's lymphoma BL41 cell lines were evaluated by flow cytometry. Apoptosis induction was assessed by two corroborative assays; propidium iodide (PI) staining of cell DNA and flow cytometric light scatter analysis. The mitochondria membrane potential was investigated using a fluorescent dye DIOC6. The expression of caspases-3, -8, -9 and PARP was assessed by Western blot. The phytochemical screening of the roots of Bryonia dioica was performed using qualitative phytochemical standard procedures.
  
  
  RESULTS
  The Bryonia dioica aqueous extract induced cell death in a dose-dependent manner. The IC50 of Bryonia dioica aqueous extract was estimated to be approximately 15, 63μg/ml. This was accompanied by induction of apoptosis, activation of caspase-3 and -9, cleavage of PARP and loss of mitochondria membrane potential. Furthermore, the phytochemical screening of roots of Bryonia dioica showed the presence of various bioactive such as polyphenols, sterols and triterpenes, alkaloids, c-heterosides, carbohydrates and saponins.
  
  
  CONCLUSIONS
  The aqueous extract of Bryonia dioica induces apoptosis in the Burkitt's lymphoma BL41 cell lines via the mitochondrial pathway. The flavonoids, sterols and triterpens detected could be responsible for the cytotoxic and apoptogenic activities of the aqueous extract of Bryonia dioica. These findings suggest that Bryonia dioica could be considered as a promising source for developing novel therapeutics against Burkitt's lymphoma.
authors.affiliation: Laboratory Research on Biological Systems and Geomatics, Faculty of Nature and Life, University of Mascara, Algeria. bachirsb@yahoo.fr
authors.forename: Bachir
authors.initials: B
authors.lastname: Benarba
authors.forename: Boumedienne
authors.initials: B
authors.lastname: Meddah
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Aoues
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D029772:Bryonia / Q000737:chemistry; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D008027:Light; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D018517:Plant Roots; D010946:Plants, Medicinal; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012542:Scattering, Radiation; D015398:Signal Transduction / Q000187:drug effects*; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D012997:Solvents; D014867:Water; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9