Brazilian green propolis induced apoptosis in human lung cancer A549 cells through mitochondrial-mediated pathway

J Pharm Pharmacol. 2015 Oct;67(10):1448-56. doi: 10.1111/jphp.12449. Epub 2015 Jul 21.


Objectives: 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.

Key findings: 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.

Keywords: apoptosis; lung cancer; mitochondria pathway; propolis.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Brazil
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Propolis / administration & dosage
  • Propolis / pharmacology*
  • Time Factors
  • Vero Cells


  • Antineoplastic Agents
  • Propolis