A monoterpene, unique component of thyme honeys, induces
apoptosis in prostate cancer cells via inhibition of NF-κB activity and IL-6
secretion
Phytomedicine, 2014 Jun 2. pii: S0944-7113(14)00216-5
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
100μM, while it inhibited NF-κB phosphorylation and IL-6 secretion at a
concentration range 10-6-10-4M. 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 0.57mg/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.
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