Propolis Extract (Bio 30) Suppresses the Growth of Human Neurofibromatosis (NF) Tumor Xenografts in Mice

PHYTOTHERAPY RESEARCH
Phytother. Res. 23, 226–230 (2009)
Published online 22 August 2008 in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/ptr.2594

* Correspondence to: Hiroshi Maruta, NF Cure Japan, 6 Shiel Street,
North Melbourne, Australia 3051.
E-mail: maruta19420@hotmail.com

CAPE (Caffeic Acid Phenethyl Ester)-basedPropolis Extract (Bio 30) Suppresses the  Growth of Human Neurofibromatosis (NF) Tumor Xenografts in Mice

M. Demestre1, S. M. Messerli2, N. Celli3, M. Shahhossini1, L. Kluwe1, V. Mautner1 and
H. Maruta1*
1UKE (Universitaets Klinikum Eppendorf), Hamburg 20246, Germany
2MBL (Marine Biological Laboratory), Woods Hole, MA 02543, USA
3Consorzio Mario Negri Sud, Via Nazionale, Chieti 66030, Italy

Dysfunction of the NF1 gene coding a RAS GAP is the major cause of neurofibromatosis type 1 (NF1), whereas
neurofibromatosis type 2 (NF2) is caused primarily by dysfunction of the NF2 gene product called merlin that
inhibits directly PAK1, an oncogenic Rac/CDC42-dependent Ser/Thr kinase. It was demonstrated previously
that PAK1 is essential for the growth of both NF1 and NF2 tumors. Thus, several anti-PAK1 drugs, including
FK228 and CEP-1347, are being developed for the treatment of NF tumors. However, so far no effective NF
therapeutic is available on the market. Since propolis, a very safe healthcare product from bee hives, contains
anticancer ingredients called CAPE (caffeic acid phenethyl ester) or ARC (artepillin C), depending on the source,
both of which block the oncogenic PAK1 signaling pathways, its potential therapeutic effect on NF tumors was
explored in vivo. Here it is demonstrated that Bio 30, a CAPE-rich water-miscible extract of New Zealand (NZ)
propolis suppressed completely the growth of a human NF1 cancer called MPNST (malignant peripheral nerve
sheath tumor) and caused an almost complete regression of human NF2 tumor (Schwannoma), both grafted in
nude mice. Although CAPE alone has never been used clinically, due to its poor bioavailability/water-solubility,
Bio 30 contains plenty of lipids which solubilize CAPE, and also includes several other anticancer ingredients
that seem to act synergistically with CAPE. Thus, it would be worth testing clinically to see if Bio 30 and other
CAPE-rich propolis are useful for the treatment of NF patients. Copyright © 2008 John Wiley & Sons, Ltd.