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

• Published in: Journal of pharmacy and pharmacology 2015-10, Vol.67 (10), p.1448-1456
• Main Authors: Frión-Herrera, Yahima, Díaz-García, Alexis, Ruiz-Fuentes, Jenny, Rodríguez-Sánchez, Hermis, Sforcin, José Maurício
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Brazil; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Cercopithecus aethiops; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic - drug effects; Genes; Humans; Inhibitory Concentration 50; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; mitochondria pathway; propolis; Propolis - administration & dosage; Propolis - pharmacology; Time Factors; Vero Cells
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12449

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.