Therapeutic Effect of Epigallocatechin-3-gallate (EGCG) and Silibinin on ATM Dynamics in Prostate Cancer Cell Line LNCaP

BACKGROUND: Epigallocatechin-3-gallate (EGCG) is a major ingredient of green tea (GT) and silibinin (SB), the active component of Silymarin presumably hold a potential to prevent pathogenomics. Prostate cancer exacerbation is triggered by fusion transcripts formed because of genomic instability induced by juxtapositioning of two genes. This chimeric transcript is implicated in androgen dependent and independent prostate cancer. Tremendous work is done on the characterization of the mediators involved in the disease refractoriness, yet no study has addressed clinical management of these prostate fusion transcripts impressively. METHODS: An abolished ATM dynamics challenges integrity of DNA. In agreement with this assumption, ATM and DNA-PK were impaired in LNCaP cell line to confirm a tight interaction of these mediators with the expression profile of TMPRSS2-ERG. Abolished ATM enhanced the expression of the fusion transcript. Similarly blunting of DNA-PK downregulated the expression of the fusion transcript giving a notion that DNA-PK is involved in the chromosomal translocation. LNCaP cell lines were analyzed for the effect of EGCG and SB on the expression profile of TMPRSS2-ERG. RESULTS: In this particular unprecedented study, treatment of the LNCaP cell line with EGCG and Silibilin recapitulated ATM expression and activity and downregulated the fusion transcript appearance. CONCLUSIONS: These results underscore the therapeutic effect of EGCG and SB in mitigating the exacerbation of the disease with reference to the fusion transcripts.