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Genome-wide transcriptome analysis of the dietary chemopreventive phytochemical sulforaphane on normal and prostate cancer cells.

ABSTRACT: Epidemiological studies provide strong evidence that consumption of cruciferous vegetables, such as broccoli, can significantly reduce the risk of developing cancers. Sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for these specific chemopreventive properties remain unclear. We utilized RNA sequencing to test the hypothesis that SFN modifies the expression of genes that are critical in prostate cancer progression. Normal prostate epithelial cells, and androgen-dependent and androgen-independent prostate cancer cells were treated with 15 µM SFN and the transcriptome was determined at 6 and 24 hour time points. SFN altered the expression of ~3,000 genes in each cell line and the response was highly dynamic over time. SFN influenced the expression of genes in functional groups and pathways that are critical in cancer including cell cycle, apoptosis and angiogenesis, but the specific effects of SFN differed depending on the state of cancer progression. Network analysis suggested that a transcription factor that is overexpressed in many cancers, Specificity protein 1 (Sp1), is a major mediator of SFN-induced changes in gene expression. Nuclear Sp1 protein was significantly decreased by 24 hour SFN treatment in prostate cancer cells, while a related transcription factor, Sp3 protein was only modestly decreased in androgen-independent prostate cancer cells. Overall, the data show that SFN significantly affects gene expression in normal and cancer cells, with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent.

ORGANISM(S): Homo sapiens

PROVIDER: GSE48812 | GEO | 2014/07/11

SECONDARY ACCESSION(S): PRJNA211827

REPOSITORIES: GEO

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Project description:Cruciferous vegetable consumption has been associated with a decreased risk of multiple types of cancers, thus presenting a cost-effective, non-pharmacological approach to cancer prevention through dietary intervention. Broccoli sprouts and Brussels sprouts are among the leading cruciferous vegetables under study and contain some similar and some distinct phytochemicals which can activate different, but complementary, mechanisms to promote health. While the cancer-preventative effects of cruciferous vegetables are typically attributed to glucosinolates and their metabolic products, isothiocyanates and indoles, other components of cruciferous vegetables could play a synergistic role in conferring cancer-protective and health promoting effects. Additionally, metabolism of phytochemicals from cruciferous vegetables by the gut microbiome could further lead to the production, inactivation, or clearance of bioactive dietary components. The gut microbiome is essential to the production of bioactive compounds from various food sources. For example, with soy isoflavones and pomegranate urolithins, the presence or absence of specific microbial taxa directly dictates which metabolites are produced (resulting in a metabotype). A similar paradigm could be extended to cruciferous vegetables in which the gut microbiome may play an important role in driving inter-individual metabolism of glucosinolates and isothiocyanates. We recently reported (Bouranis et. al, 2021, Nutrients) that the gut microbiome composition can influence production of glucosinolate-derived nitriles from cruciferous vegetables, showing that the presence or absence of specific microbes can influence the abundance of a single metabolite. Thus, we sought to take an untargeted approach to investigate other phytochemicals from cruciferous vegetables which the gut microbiome could play a role in generating. To investigate plant- and microbe-derived metabolites of cruciferous vegetable digestion and capture information about the microbiome, we utilized an ex vivo fecal incubation system. Broccoli sprouts and Brussels sprouts were in vitro digested using an oral, gastric, and intestinal phase. For fecal bacterial cultivation a 20% fecal slurry (w/v) was made from fecal material from 10 healthy volunteers (6 female, and 4 male, age 17-51, Lee Biosolutions) and sterile PBS (0.1 M pH 7). 500 µL of fecal slurry was mixed with 10 mL of Brain Heart Infusion Broth (BHI) with hemin and vitamin K, per the manufacturer’s recommendation, and either 500 µl of filter sterilized in vitro digested broccoli sprouts (Broc), 500 µL of filter sterilized in vitro digested Brussels sprouts (Brus), 500 µL of Broc and 500 µL of Brus were added (Combo) or a negative control in vitro digestion (NC). NC contained reverse osmosis water, equivalent in volume to the water content of broccoli sprouts and underwent the same in vitro digestion procedure as described above with the same enzymes, chemicals and equipment. Broc and Brus digests were scaled to be equivalent in concentration to a human consuming ½ cup of broccoli or Brussels sprouts, or in the case of the combination, ½ cup of broccoli sprouts and ½ cup of Brussels sprouts. This combination was included as Broc and Brus contain many similar but also some distinct phytochemicals and thus by combining the vegetables we increased the dose and broadened the range of phytochemicals from cruciferous vegetables which can be achieved in the kitchen as a mixed vegetable dish. Fecal cultures were incubated at 37°C for 24 h in anaerobic conditions.

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Genome-wide transcriptome analysis of the dietary chemopreventive phytochemical sulforaphane on normal and prostate cancer cells.

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