title: Sulforaphane Inhibits c-Myc-Mediated Prostate Cancer Stem-Like Traits.
abstract: Preventive and therapeutic efficiencies of dietary sulforaphane (SFN) against human prostate cancer have been demonstrated in vivo, but the underlying mechanism(s) by which this occurs is poorly understood. Here, we show that the prostate cancer stem cell (pCSC)-like traits, such as accelerated activity of aldehyde dehydrogenase 1 (ALDH1), enrichment of CD49f+ fraction, and sphere forming efficiency, are attenuated by SFN treatment. Interestingly, the expression of c-Myc, an oncogenic transcription factor that is frequently deregulated in prostate cancer cells, was markedly suppressed by SFN both in vitro and in vivo. This is biologically relevant, because the lessening of pCSC-like phenotypes mediated by SFN was attenuated when c-Myc was overexpressed. Naturally occurring thio, sulfinyl, and sulfonyl analogs of SFN were also effective in causing suppression of c-Myc protein level. However, basal glycolysis, a basic metabolic pathway that can also be promoted by c-Myc overexpression, was not largely suppressed by SFN, implying that, in addition to c-Myc, there might be another SFN-sensitive cellular factor, which is not directly involved in basal glycolysis, but cooperates with c-Myc to sustain pCSC-like phenotypes. Our study suggests that oncogenic c-Myc is a target of SFN to prevent and eliminate the onset of human prostate cancer. J. Cell. Biochem. 117: 2482-2495, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh 15213, Pennsylvania.
authors.forename: Avani R
authors.initials: AR
authors.lastname: Vyas
authors.affiliation: Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh 15213, Pennsylvania.
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Moura
authors.affiliation: Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh 15213, Pennsylvania.
authors.forename: Eun-Ryeong
authors.initials: ER
authors.lastname: Hahm
authors.affiliation: Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh 15213, Pennsylvania.
authors.forename: Krishna Beer
authors.initials: KB
authors.lastname: Singh
authors.affiliation: Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh 15213, Pennsylvania. singhs@upmc.edu.
authors.forename: Shivendra V
authors.initials: SV
authors.lastname: Singh
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013454:Sulfoxides; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013454:Sulfoxides; C016766:sulforaphane
keywords: CHEMOPREVENTION; PROSTATE CANCER STEM CELLS; SULFORAPHANE; c-MYC