Co-administration of apigenin with doxorubicin enhances anti-migration and antiproliferative effects via PI3K/PTEN/AKT pathway in prostate cancer cells.

Abstract

The effect of the treatment on survival and migration of human PC3cells was evaluated by MTT and scratch assay, respectively. Apoptosis and cell cycle distribution were detected by image-based cytometry. mRNA and protein expression were determined by real-time quantitative polymerase chain reaction and Western blot, respectively. Apigenin and doxorubicin dose-dependently inhibited cell survival, and co-administration of both agents significantly induced cell death via upregulating the mRNA expression of caspases, Bax and cytochrome c, and downregulating Bcl-XL. Combination therapy caused cell cycle arrest by upregulating the expression of p21and p27. The treatment modality inhibited cell migration via downregulating Snail, Twist and MMPs in which doxorubicin was ineffective. Apigenin dephosphorylated Akt strongly, significantly suppressed ERK phosphorylation, and increased PTEN expression 4.5-fold. The combination of apigenin and doxorubicin inhibited PI3K and AKT phosphorylation more strongly than a single administration. Our data indicate that a combination of the natural flavone apigenin with doxorubicin might have a potential in treatment of castration-resistant prostate cancer.