Volume 21, Issue 11, 25 September 2014, Pages 1483–1489
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.
Abbreviations
- NF-κB, nuclear factor-kappaB;
- mapk, mitogen-activated protein kinase;
- PI3K, phosphatidylinositide 3-kinase;
- Akt, protein kinase B;
- FAK, focal adhesion kinase;
- PSG, prostate-specific G-protein-coupled receptor;
- IL-6, interleukin-6;
- JNK, c-Jun NH(2)-terminal kinase;
- TLC, thin layer chromatography;
- NMR, nuclear magnetic resonance;
- FBS, fetal bovine serum;
- DCC, dextran coated charcoal slurry;
- RT, room temperature;
- GC-MS, gas chromatography–mass spectrometry;
- MIC, minimum inhibitory concentration;
- AIDS, acquired immunodeficiency syndrome;
- PI, propidium iodide;
- RI, retention indices;
- AP-1, activator protein 1;
- CREB, cAMP response element-binding protein;
- c/EBP, CCAAT/enhancer binding protein;
- SAPK, stress-activated protein kinases
Keywords
- Apoptosis;
- Interleukin-6;
- Monoterpene;
- NF-κB;
- Prostate cancer cells;
- Trihydoxy ketone
Copyright © 2014 Elsevier GmbH. All rights reserved.