S-Adenosylmethionine affects ERK1/2 and STAT3 pathway in androgen-independent prostate cancer cells

Abstract

Abstract Background The most critical point in the treatment of prostate cancer is the progression towards a hormone-refractory tumour, making research on alternative therapies necessary. This study focused on the methyl donor S-adenosylmethionine (SAM), which is known to act as an antitumourigenic in several cancer cell lines. Though a genome-wide downregulation of proto-oncogenes in prostate cancer cell lines treated with SAM is obvious, the anticancer effects remain elusive. Thus, in this study, the impact of SAM treatment on the cell cycle, apoptosis and cancer-related pathways was investigated. Methods and results After performing SAM treatment on prostate cancer cell lines (PC-3 and DU145), a cell-cycle arrest during the S-phase, a downregulation of cyclin A protein levels and an upregulation of p21 cell cycle inhibitor were observed. The proapoptotic Bax/Bcl-2 ratio and the caspase-3 activity were elevated; additionally, the apoptosis rate of SAM treated cells increased significantly in a time-dependent manner. Moreover, immunoblots displayed a downregulation of Erk1/2 and STAT3 phosphorylation accompanied by a reduced expression of the STAT3 protein. Conclusion SAM caused changes in cancer-related pathways, probably leading to the effects on the cell cycle and apoptosis rate. These results provide deeper insights into the anticancer effects of SAM on prostate cancer cells.