Epigenetic mechanism of growth inhibition induced by phenylhexyl isothiocyanate in prostate cancer cells.

BACKGROUND: Isothiocyanates, the constituents of cruciferous vegetables, may be able to prevent prostate cancer. The hypothesis that they could remodel chromatins and activate cell cycle inhibitors, such as p21 for growth inhibition, was tested. MATERIALS AND METHODS: Prostate cancer LNCaP cells were exposed to phenylhexyl isothiocyanate (PHI). The status of histone acetylation and the activity of histone deacetylases (HDAC) were investigated. The association of p21 with hyperacetylated histones was examined by chromatin immunoprecipitation. RESULTS: The PHI-exposed LNCaP cells had diminished activity of HDAC 1 and 2. Global and selective histone acetylation was enhanced, consistent with the signs of chromatin unfolding. The hyperacetylated histones increased accessibility to the p21 promoter for transcription, leading to G1 arrest and apoptosis. CONCLUSION: PHI inhibited the activity of HDAC and remodeled chromatins to activate p21 for cell cycle arrest, underlying an epigenetic mechanism regulating the growth of prostate cancer cells.

Modulating testosterone stimulated prostate growth by phenethyl isothiocyanate via Sp1 and androgen receptor down-regulation.

BACKGROUND: The effects of phenethyl isothiocyanate (PEITC), present naturally in cruciferous vegetables, on androgen-influenced growth of the prostate such as benign hyperplasia, was investigated. METHODS: Rats dosed with cyproterone acetate and testosterone, were fed at the same time with either PEITC or vehicle control. The growth of the prostates was compared to untreated rats. RESULTS: While testosterone increased the prostate mass (30%) and hyperplastic seminiferous tubules as compared to the untreated rats, PEITC feeding decreased the prostate mass and hyperplasia to roughly the levels of untreated rats (P < 0.05). PEITC negated the testosterone-mediated enhancement of the androgen receptor (AR), via down-regulating transcription factor Sp1 expression and Sp1 binding complex formation. Cell cycle progression was attenuated with decreases of cyclins, Rb, and up-regulates p27. CONCLUSIONS: PEITC modulates the testosterone-influenced growth by repressing Sp1, thus down-regulating AR and proliferation. PEITC from cruciferous vegetables may represent a regulator for hormone-dependent growth of the prostate.

Borrelia burgdorferi binds to, invades, and colonizes native type I collagen lattices.

Borrelia burgdorferi binds strongly to the extracellular matrix and cells of the connective tissue, a binding apparently mediated by specific proteins and proteoglycans. We investigated the interactions between B. burgdorferi cells and intact type I collagen using hydrated lattices that reproduce features of in vivo collagen matrices. B. burgdorferi cells of several strains adhered avidly to these acellular matrices by a mechanism that was not mediated by decorin or other proteoglycans. Moreover, following adhesion to these matrices, B. burgdorferi grew and formed microcolonies. The collagen used in these studies was confirmed to lack decorin by immunoblot analysis; B. burgdorferi cells lacking the decorin adhesin bound readily to intact collagen matrices. B. burgdorferi also bound to collagen lattices that incorporated enzymes that degraded glycosaminoglycan chains in any residual proteoglycans. Binding of the bacteria to intact collagen was nonetheless specific, as bacteria did not bind agar and showed only minimal binding to bovine serum albumin, gelatin, pepsinized type I collagen, and intact collagen that had been misassembled under nonphysiological pH and ionic-strength conditions. Proteinase K treatment of B. burgdorferi cells decreased the binding, as did a lack of flagella, suggesting that surface-exposed proteins and motility may be involved in the ability of B. burgdorferi to interact with intact collagen matrices. The high efficiency of binding of B. burgdorferi strains to intact collagen matrices permits replacement of the commonly used isotopic binding assay with visual fluorescent microscopic assays and will facilitate future studies of these interactions.