title: A monoterpene, unique component of thyme honeys, induces apoptosis in prostate cancer cells via inhibition of NF-κB activity and IL-6 secretion.
abstract: We have previously demonstrated that Greek thyme honey inhibits significantly the cell viability of human prostate cancer cells. Herein, 15 thyme honey samples from several regions of Greece were submitted to phytochemical analysis for the isolation, identification and determination (through modern spectral means) of the unique thyme honey monoterpene, the compound trihydroxy ketone E-4-(1,2,4-trihydroxy-2,6,6-trimethylcyclohexyl)-but-3-en-2-one. We investigated the anti-growth and apoptotic effects of the trihydroxy ketone on PC-3 human androgen independent prostate cancer cells using MTT assay and Annexin V-FITC respectively. The molecular pathways involved to such effects were further examined by evaluating its ability to inhibit (a) the NF-κB phosphorylation (S536), (b) JNK and Akt phosphorylation (Thr183/Tyr185 and S473 respectively) and (c) IL-6 production, using ELISA method. The anti-microbial effects of the trihydroxy ketone against a panel of nine pathogenic bacteria and three fungi were also assessed. The trihydroxy ketone exerted significant apoptotic activity in PC-3 prostate cancer cells at 100 μM, while it inhibited NF-κB phosphorylation and IL-6 secretion at a concentration range 10(-6)-10(-4)M. Akt and JNK signaling were not found to participate in this process. The trihydroxy ketone exerted significant anti-microbial profile against many human pathogenic bacteria and fungi (MIC values ranged from 0.04 to 0.57 mg/ml). Conclusively, the Greek thyme honey-derived monoterpene exerted significant apoptotic activity in PC-3 cells, mediated, at least in part, through reduction of NF-κB activity and IL-6 secretion and may play a key role in the anti-growth effect of thyme honey on prostate cancer cells.
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens, 75 Mikras Asias Str., 11527 Goudi, Athens, Greece. Electronic address: ekassi@med.uoa.gr.
authors.forename: Eva
authors.initials: E
authors.lastname: Kassi
authors.affiliation: Division of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis-Zografou, 15771 Athens, Greece. Electronic address: ichinou@pharm.uoa.gr.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Chinou
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens, 75 Mikras Asias Str., 11527 Goudi, Athens, Greece.
authors.forename: Eliana
authors.initials: E
authors.lastname: Spilioti
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens, 75 Mikras Asias Str., 11527 Goudi, Athens, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Tsiapara
authors.affiliation: Division of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis-Zografou, 15771 Athens, Greece.
authors.forename: Konstantia
authors.initials: K
authors.lastname: Graikou
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens, 75 Mikras Asias Str., 11527 Goudi, Athens, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Karabournioti
authors.affiliation: Department of Pathophysiology, Medical School, University of Athens, 75 Mikras Asias Str., 11527 Goudi, Athens, Greece.
authors.forename: Menelaos
authors.initials: M
authors.lastname: Manoussakis
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens, 75 Mikras Asias Str., 11527 Goudi, Athens, Greece. Electronic address: pmoutsatsou@med.uoa.gr.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Moutsatsou
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006115:Greece; D006722:Honey; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007659:Ketones / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008826:Microbial Sensitivity Tests; D039821:Monoterpenes / Q000494:pharmacology*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D046930:Thymus Plant / Q000737:chemistry; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; C508600:IL6 protein, human; D015850:Interleukin-6; D007659:Ketones; D039821:Monoterpenes; C498143:RELA protein, human; D051996:Transcription Factor RelA; D051057:Proto-Oncogene Proteins c-akt
keywords: Apoptosis; Interleukin-6; Monoterpene; NF-κB; Prostate cancer cells; Trihydoxy ketone