Kermanian propolis induces apoptosis through upregulation of Bax/Bcl-2 ratio in acute myeloblastic leukemia cell line (NB4)

Propolis is a viscous resinous honeybee-produced substance with numerous medicinal functions; its composition and texture varies according to the geographic location. It is considered to be a promising natural source for the management and prevention of various pathological conditions. Although several studies have exhibited the anti-cancer activity of different types of propolis, the tumor-suppressing potential of Kermanian propolis against leukemia cell lines has remained poorly understood. Therefore, the current experiment was aimed to reveal the anti-tumor activity of this bioactive compound both as monotherapy and combined therapy with cytarabine against an acute myeloid leukemia (AML) cell line, NB4. Following the treatment of NB4 cells with either Kermanian propolis (5, 10, 20, 40, 80, 160, and 320 μg/mL), cytarabine (0.1, 0.25, 0.5, 0.75, 1, and 2 mM), or their combination (40 and 80 μg/mL of Kermanian propolis along with 0.1, 0.25, and 0.5 mM of cytarabine), colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to measure the viability (%) of the cells. Next, to examine the apoptotic rate and the pattern of corresponding gene expression (Bcl-2, Bax, p53, and p21), Annexin-V/PI staining by flow cytometry and quantitative Real-Time polymerase chain reaction assays were performed, respectively. We perceived significant apoptosis induction in a dose-dependent manner following the treatment with Kermanian propolis, cytarabine, and also their combination in the NB4 cell line. In addition, the combined treatment was associated with lower expression of the anti-apoptotic gene (Bcl-2) and higher expression of the pro-apoptotic genes (p53, Bax, and p21) in comparison to mono treatments. The synergistic anti-tumor activity induced by the combination of Kermanian propolis and cytarabine presents a novel and encouraging option for AML treatment.