Temporal changes in gene expression induced by sulforaphane in human prostate cancer cells.
BACKGROUND
Prostate cancer is thought to arise as a result of oxidative stresses and induction of antioxidant electrophile defense (phase 2) enzymes has been proposed as a prostate cancer prevention strategy. The isothiocyanate sulforaphane, derived from cruciferous vegetables like broccoli, potently induces surrogate markers of phase 2 enzyme activity in prostate cells in vitro and in vivo. To better understand the temporal effects of sulforaphane and broccoli sprouts on gene expression in prostate cells, we carried out comprehensive transcriptome analysis using cDNA microarrays.


METHODS
Transcripts significantly modulated by sulforaphane over time were identified using StepMiner analysis. Ingenuity Pathway Analysis (IPA) was used to identify biological pathways, networks, and functions significantly altered by sulforaphane treatment.


RESULTS
StepMiner and IPA revealed significant changes in many transcripts associated with cell growth and cell cycle, as well as a significant number associated with cellular response to oxidative damage and stress. Comparison to an existing dataset suggested that sulforaphane blocked cell growth by inducing G2/M arrest. Cell growth assays and flow cytometry analysis confirmed that sulforaphane inhibited cell growth and induced cell cycle arrest.


CONCLUSIONS
Our data suggest that in prostate cells sulforaphane primarily induces cellular defenses and inhibits cell growth by causing G2/M phase arrest. Furthermore, based on the striking similarities in the gene expression patterns induced across experiments in these cells, sulforaphane appears to be the primary bioactive compound present in broccoli sprouts, suggesting that broccoli sprouts can serve as a suitable source for sulforaphane in intervention trials.
Bhamre
Suvarna
S
Department of Urology, Stanford University, Stanford, California 4305-5118, USA.
Sahoo
Debashis
D
Tibshirani
Robert
R
Dill
David L
DL
Brooks
James D
JD
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D017879:Isothiocyanates; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D014158:Transcription, Genetic
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D009363:Neoplasm Proteins; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane