Τίτλος:
A monoterpene, unique component of thyme honeys, induces apoptosis in prostate cancer cells via inhibition of NF-κB activity and IL-6 secretion
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2014 Elsevier GmbH. All rights reserved.
Συγγραφείς:
Kassi, E.
Chinou, I.
Spilioti, E.
Tsiapara, A.
Graikou, K.
Karabournioti, S.
Manoussakis, M.
Moutsatsou, P.
Εκδότης:
Urban und Fischer Verlag Jena
Λέξεις-κλειδιά:
4 (1,2,4 trihydroxy 2,6,6 trimethylcyclohexyl) but 3 en 2 one; antiinfective agent; antineoplastic agent; dexamethasone; flucytosine; fluorescein isothiocyanate; immunoglobulin enhancer binding protein; interleukin 6; itraconazole; ketone derivative; lipocortin 5; netilmicin; protein kinase B; stress activated protein kinase; terpene; threonine; tyrosine; unclassified drug; antiinfective agent; antineoplastic agent; IL6 protein, human; interleukin 6; ketone; protein kinase B; RELA protein, human; terpene; transcription factor RelA, antibacterial activity; antifungal activity; antimicrobial activity; apoptosis; article; cancer inhibition; concentration response; controlled study; cytokine production; cytokine release; drug effect; drug identification; drug isolation; drug mechanism; drug structure; enzyme linked immunosorbent assay; fungus; Gram negative bacterium; Gram positive bacterium; Greece; honey; human; human cell; minimum inhibitory concentration; MTT assay; nonhuman; phytochemistry; priority journal; prostate cancer cell line; protein phosphorylation; signal transduction; thyme; apoptosis; cell survival; chemistry; drug effects; male; metabolism; microbial sensitivity test; phosphorylation; prostate tumor; secretion (process); Thymus (plant); tumor cell line, Fungi; Thymus vulgaris, Anti-Bacterial Agents; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Greece; Honey; Humans; Interleukin-6; Ketones; Male; MAP Kinase Signaling System; Microbial Sensitivity Tests; Monoterpenes; Phosphorylation; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Thymus Plant; Transcription Factor RelA
DOI:
10.1016/j.phymed.2014.04.032
