title: Psidium guajava L. anti-neoplastic effects: induction of apoptosis and cell differentiation.
abstract: OBJECTIVE
  Curative properties of medicinal plants such as Psidium guajava L. (Myrtaceae) have often been indicated by epidemiological studies on populations in which these fruits are consumed daily. However, complete characterization of the active principles responsible for this ability has never been performed. Here, we have characterized P. guajava's anti-cancer potential and identified the parts of the fruit involved in its anti-neoplastic action.
  
  
  METHODS
  We studied morphology of our cells, cell cycle characteristics and apoptosis and performed immunostaining, differentiation and western blot analyses.
  
  
  RESULTS
  We report that the P. guajava extract exerted anti-cancer control on both haematological and solid neoplasias. P. guajava extract's anti-tumour properties were found to be tightly bound to induction of apoptosis and differentiation. Use of ex vivo myeloid leukaemia blasts corroborated that P. guajava was able to induce cell death but did not exhibit anti-cancer effects on all malignant cells investigated, indicating selective activity against certain types of tumour. Analyses of P. guajava pulp, peel and seeds identified the pulp as being the most relevant component for causing cell cycle arrest and apoptosis, whereas peel was responsible for causing cell differentiation. P. guajava itself and its pulp-derived extract were found to induce apoptosis accompanied by caspase activation and p16, p21, Fas ligand (FASL TNF super-family, member 6), Bcl-2-associated agonist of cell death (BAD) and tumour necrosis factor receptor super-family, member 10b (DR5), overexpression.
  
  
  CONCLUSIONS
  Our findings showed that P. guajava L. extract was able to exert anti-cancer activity on cultures in vitro and ex vivo, supporting the hypothesis of its anti malignant pro-apoptotic modulation.
authors.affiliation: Dipartimento di Patologia generale, Seconda Università degli Studi di Napoli, Napoli, Italy. paola.bontempo@unina2.it
authors.forename: P
authors.initials: P
authors.lastname: Bontempo
authors.forename: A
authors.initials: A
authors.lastname: Doto
authors.forename: M
authors.initials: M
authors.lastname: Miceli
authors.forename: L
authors.initials: L
authors.lastname: Mita
authors.forename: R
authors.initials: R
authors.lastname: Benedetti
authors.forename: A
authors.initials: A
authors.lastname: Nebbioso
authors.forename: M
authors.initials: M
authors.lastname: Veglione
authors.forename: D
authors.initials: D
authors.lastname: Rigano
authors.forename: M
authors.initials: M
authors.lastname: Cioffi
authors.forename: V
authors.initials: V
authors.lastname: Sica
authors.forename: A M
authors.initials: AM
authors.lastname: Molinari
authors.forename: L
authors.initials: L
authors.lastname: Altucci
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D031647:Psidium; D020298:U937 Cells
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D010936:Plant Extracts; D020169:Caspases