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

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

Author information

1
Department of Microbiology and Immunology, Biosciences Institute, UNESP, Botucatu, São Paulo, Brazil.
2
Laboratories of Biofarmaceuticals and Chemistries Productions (LABIOFAM), Havana, Cuba.
3
Tropical Medicine Institute Pedro Kouri, Havana, Cuba.

Abstract

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

PMID:
26206395
DOI:
10.1111/jphp.12449
[Indexed for MEDLINE]

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