title: Brazilian green propolis induced apoptosis in human lung cancer A549 cells through mitochondrial-mediated pathway.
abstract: OBJECTIVE
  Propolis effect on the growth and apoptosis of human lung adenocarcinoma (A549 cells) was investigated as well as its mechanisms.
  
  
  METHODS
  Cells were incubated with propolis for 72 h, and 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays were employed to assess cell viability and the inhibitory concentration (IC). Apoptosis was detected by Acridine Orange/Ethidium Bromide and 4',6-diamidino-2-phenylindole staining after 24 and 48 h of incubation with ¼ IC50 of propolis by testing the mitochondrial membrane potential (ΔΨm) and the expression of apoptosis-related genes (p53, Caspase-3, Bax, Bcl-2, Bcl-XL , Noxa, Puma and p21) by reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Propolis displayed antiproliferative and cytotoxic effects on A549 cells in a dose- and time-dependent manner, but it did not suppress the growth of normal Vero cells. An enhanced apoptosis was seen in A549 propolis-treated cells after 48 h compared with the control cells. Propolis decreased mitochondrial membrane potential by overexpression of pro-apoptotic genes (Bax and Noxa) and reduction of the antiapoptotic gene Bcl-XL . The expression level of other genes remained unchanged (p53, Caspse-3 and Bax), whereas p21 expression was increased. Propolis induced caspase-independent apoptosis through a p53-independent mitochondrial pathway, and cell cycle arrest by upregulation of p21.
  
  
  CONCLUSIONS
  Although propolis induces apoptosis mainly by p53-independent manner, it may be induced by another pathway, and new insights may arise for preventing or treating lung cancer.
authors.affiliation: Department of Microbiology and Immunology, Biosciences Institute, UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Yahima
authors.initials: Y
authors.lastname: Frión-Herrera
authors.affiliation: Laboratories of Biofarmaceuticals and Chemistries Productions (LABIOFAM), Havana, Cuba.
authors.forename: Alexis
authors.initials: A
authors.lastname: Díaz-García
authors.affiliation: Tropical Medicine Institute Pedro Kouri, Havana, Cuba.
authors.forename: Jenny
authors.initials: J
authors.lastname: Ruiz-Fuentes
authors.affiliation: Tropical Medicine Institute Pedro Kouri, Havana, Cuba.
authors.forename: Hermis
authors.initials: H
authors.lastname: Rodríguez-Sánchez
authors.affiliation: Department of Microbiology and Immunology, Biosciences Institute, UNESP, Botucatu, São Paulo, Brazil.
authors.forename: José Maurício
authors.initials: JM
authors.lastname: Sforcin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001938:Brazil; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D011429:Propolis / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014709:Vero Cells
chemical_list: D000970:Antineoplastic Agents; D011429:Propolis
keywords: apoptosis; lung cancer; mitochondria pathway; propolis