Krebswissenschaft und -therapie

Ellagic acid is an antioxidant and an anti-proliferative compound present in fruits, nuts and vegetables. In spite of evidences for anticancer activity in various cancer cell-lines, human cancer cells, the mechanistic role of ellagic acid is not conclusive enough to be recommended for a clinical use. The present review provides information about the chemopreventive role of ellagic acid in oral cancer and proposes molecular basis for ellagic acid’s inhibitory activity against oral cancer. We show that ellagic acid modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin dependent kinase 2, cyclin A2, cyclin B1, cyclin D1, c-myc, PKCα), cell survival/apoptosis pathway (Bcl-XL, Bax, Caspase 9/3, Akt), tumor suppressor pathway (p53, p21), inflaming Metastasis pathways (IL-1 beta, TNF-α, matrix metalloproteinases 9/3, COX-2), angiogenesis pathways (VEGF), cell immortalization (TERT), NF-κβ.

Background:The purpose of this study was to investigate the association between haplotype-tagging single nucleotide polymorphisms (SNPs) within the Aurora Kinase A (AURKA) gene and prostate cancer outcomes in patients with clinically localized prostate cancer.

Methods:Four intronic haplotype-tagging SNPs within the AURKA gene were individually selected and examined in regard to their influence on clinical outcomes in 212 patients who underwent radical prostatectomy as first-line treatment. Haplotype-tagging SNPs were selected using the ABI SNP Browser to cover SNPs with an r2 of 0.90 or greater in the AURKA gene with a minor allele frequency of at least 0.25.

Results:In our study, a log-rank univariate analysis was performed to identify significant associations between probability of recurrence-free survival or disease-free survival and known prognostic indicators as well as AURKAgenotypes. The prognostic indicators Gleason grade, surgical margin, extracapsular extension, and disease stage were associated with recurrence-free survival (all p<0.001). Only Gleason grade was associated with disease-free survival (p<0.001). No associations were found for the SNPs rs1468055, rs8117896, rs2064863, and rs1468056analyzed for either RFS (p=0.7213, p=0.5140, p=0.0714, p=0.4731, respectively) or DFS (p=0.3282, p=0.1909, p=0.4111, p=0.5014, respectively).

Conclusions:This study demonstrates no evidence for intronic AURKA SNPs in predicting recurrence-free survival in patients with prostate cancer.