Down-regulation of phosphoglucomutase 3 mediates sulforaphane-induced cell death in LNCaP prostate cancer cells

SFN exerted cytotoxicity and increased TUNEL positive cells in a concentration-dependent manner in LNCaP cells. Proteomics study revealed that levels of nine proteins including tubulin β-2, phosphoglucomutase-3 (PGM3), melanoma-derived leucine zipper containing extra-nuclear factor, activin A type I receptor precursor, smoothelin-A, KIA0073, hypothetical protein LOC57691 and two unnamed proteins were changed over 8 folds in SFN treated LNCaP cells compared to untreated control. We have further confirmed that SFN reduced PGM3 expression with western blotting and showed that PGM3 siRNA enhanced cytotoxicity demonstrated by cell morphology and TUNEL assays in LNCaP cells.Taken together, these findings suggest that PGM3 plays a role in mediating SFN-induced cell death in LNCaP cells, and is a potential molecular therapeutic target for prostate cancer.Cell death is defined as an irreversible loss of plasma membrane integrity. Historically, three types of cell death have been distinguished in mammalian cells by morphological criteria, namely apoptosis, autophagy and necrosis [1]. Apoptosis represents a major regulatory mechanism that eliminates abundant and unwanted cells during embryonic development, growth, differentiation and normal cell turnover [2,3]. Recently, targeting apoptosis is thought to be a potential therapeutic approach for cancer treatment.Prostate cancer develops in nearly 30% of all men above the age of 50 years [4] and may metastasize to other parts of the human body, especially bones and lymph nodes. Many chemotherapeutic agents such as Eulexin, Flutamide and Nilandron have been developed for the treatment of prostate cancer. However, undesirable side effects such as urinary incontinence and erectile dysfunction can reduce the therapeutic efficacy of prostate cancer. In this regard, recent reports have reported the possibility to use natural compounds as chemopreventive candidates by inducing apoptotic cell death in prostate cancer cells [5-9].Sulforap