The isothiocyanate sulforaphane is a promising molecule for development as a therapeutic agent for patients with metastatic prostate cancer. Sulforaphane induces apoptosis in advanced prostate cancer cells, slows disease progression in vivo and is well tolerated at pharmacological doses. However, the underlying mechanism(s) responsible for cancer suppression remain to be fully elucidated. In this investigation we demonstrate that sulforaphane induces posttranslational modification of histone methyltransferase SUV39H1 in metastatic, androgen receptor-negative PC3 prostate cancer cells. Sulforaphane stimulates ubiquitination and acetylation of SUV39H1 within a C-terminal nuclear localization signal peptide motif and coincides with its dissociation from chromatin and a decrease in global trimethyl-histone H3 lysine 9 (H3K9me3) levels. Exogenous SUV39H1 expression leads to an increase in H3K9me3 and decreases sulforaphane-induced apoptotic signaling. SUV39H1 is thus identified as a novel mediator of sulforaphane cytotoxicity in PC3 cells. Our results also suggest SUV39H1 dynamics as a new therapeutic target in advanced prostate cancers.

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Glass wool, nonabsorbent cotton, fiberglass filter medium, and a commercial absolute filter were tested for effectiveness in removing aerosolized bacterial viruses under low flow rate (1 ft 3 /min) and high flow rate (10 to 25 ft 3 /min) air-flow conditions. Special equipment was designed for measurement of filter efficiencies under the two air-flow conditions. Under low air-flow rate test conditions, glass wool was only 98.543 to 99.83% efficient, whereas cotton (five layers), fiberglass medium (three layers), and the commercial absolute filter were at least 99.900, 99.999, and 99.999 efficient, respectively. Glass wool and cotton were not used under higher air-flow conditions because they were difficult to assemble in leak-tight filters. The commercial absolute filter and fiberglass medium (three layers) were at least 99.990 and 99.999% efficient, respectively, under the higher air flow conditions. A stainless-steel filter of simple design and fitted with three layers of fiberglass medium was found to be greater than 99.999% efficient in removing high concentrations (20,000 to 70,000 plaque-forming units per cubic foot) of aerosolized bacteriophages from air moving at a low flow rate (1 ft 3 /min). Use of this filter on pressure-vacuum tanks in the fermentation industry is suggested. Several other uses of such a filter are proposed.

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Sulforaphane (SFN) supplementation is well tolerated and exhibits cancer‐selective cytotoxicity in preclinical models. SFN decreases global DNA‐methyltransferase (DNMT) and histone deacetylase (HDAC) activity in prostate cancer (PCa) cells, two classes of chromatin modifying enzymes (CME) involved in heterochromatin (HC) establishment and stability. HC marks co‐occur due to coordinated CME activity; therefore, we hypothesized that deficiencies in DNMT and HDAC activity would lead to alterations in histone methyltransferase (HMT) activity. SFN (15 µM) led to a global decrease in histone H3 lysine 9 trimethylation (H3K9me3) in PC3 PCa cells. Investigation into the underlying mechanism suggests SFN influences the H3K9 HMT SUV39H1. SFN leads to SUV39H1 ubiquitination and acetylation, posttranslational marks that are associated with SUV39H1 instability and reduced enzymatic activity. SUV39H1 modification coincided with decreased HC stability. Inhibition of SUV39H1 activity by small molecule inhibitor is cytotoxic to PCa cells, suggesting SUV39H1 inactivation contributes to the cancer‐suppressive activity associated with SFN. Our results suggest that destabilization of HC plays an active role in mediating cytotoxicity in response to SFN and supports further development of SFN as a therapeutic option and SUV39H1 as a therapeutic target for PCa. Grant Funding Source: Supported by NIH P01 CA090890