Signaling pathways of docosahexenoic acid-induced apoptosis of prostate cancer cells

Abstract

Objective To explore how docosahexenoic acid (DHA) changes apoptosis signaling pathways to further lead to apoptosis of prostate cancer cells. Methods RT2 Profiler PCR Arrays were used to screen the targets of DHA-induced prostate cancer cells apoptosis (10 apoptosis genes were up-regulated and 5 apoptosis genes were down-regulated). Real-time quantitative polymerase chain reaction (Real-time PCR) was used as reliable tools to validate the results. Results As compared with bovine serum albumin (BSA), after incubation with DHA for 24 h, the transcriptional level of Caspase family: Caspase-1, Caspase-3 and Caspase-9 in DU145 cells were increased 2.06, 4.88 and 12.10 times respectively; The transcriptional level of pro-apoptotic genes B cell lymphoma/leukemia-2 associated X protein (bax) was increased 2.93 times and B cell lymphoma/leukemia-2 (bcl-2)/bax ratio increased. Cell death inducing related genes CIDEA and DFFA were increased 2.34, 3.21 times respectively; Tumor necrosis factor related genes LTA and tumor necrosis factor (TNF) were increased 2.04 and 2.24 times respectively; The expression of tumor protein P53 (TP53) gene mRNA increased 2.97 times. In addition, as compared with the BSA control group, after incubation with DHA for 24 h, the transcriptional levels of apoptosis inducing factor 1 (AIFM1), Akt1, BH3 locus death inducing gene (BID), BIRC6 and X-linked inhibitor of apoptosis protein (XIAP) were decreased. After DHA treatment for 24 h, the mRNA expression of Caspase-1, Caspase-3, Caspase-9 and Caspase-12 was increased respectively. Moreover, the expression of Caspase-3, Caspase-9 and Caspase-12 had a dose-dependent relationship with DHA concentration. The mRNA expression of bax, CIDEA, DFFA, TP53 and TNF normalized with TATA box binding protein (TBP) in 24 h DHA-treated DU145 cells was increased obviously, and the expression of bax, CIDEA and TNF had a dose-dependent relationship with DHA concentration. The mRNA expression of AIFM1, protein kinase B (Akt1), BID, BIRC6 and XIAP was decreased obviously after incubation with different concentrations of DHA for 24 h, and the expression of bax, CIDEA and TNF had a dose-dependent relationship with DHA concentration. Conclusion DHA can change the related genes expression of apoptosis signaling pathways in Caspase family, by this way it can induce the apoptosis of prostate cancer cells. Key words: Prostatic carcinoma; Androgen resistance prostate cancer; Polyunsaturated fatty acids; Docosahexenoic acid