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

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PHYTOTHERAPY RESEARCHPhytother. 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:

 
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 andH. Maruta1*1UKE (Universitaets Klinikum Eppendorf), Hamburg 20246, Germany2MBL (Marine Biological Laboratory), Woods Hole, MA 02543, USA3Consorzio 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), whereasneurofibromatosis type 2 (NF2) is caused primarily by dysfunction of the NF2 gene product called merlin thatinhibits directly PAK1, an oncogenic Rac/CDC42-dependent Ser/Thr kinase. It was demonstrated previouslythat PAK1 is essential for the growth of both NF1 and NF2 tumors. Thus, several anti-PAK1 drugs, includingFK228 and CEP-1347, are being developed for the treatment of NF tumors. However, so far no effective NFtherapeutic is available on the market. Since propolis, a very safe healthcare product from bee hives, containsanticancer 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 wasexplored 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 nervesheath tumor) and caused an almost complete regression of human NF2 tumor (Schwannoma), both grafted innude 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 ingredientsthat seem to act synergistically with CAPE. Thus, it would be worth testing clinically to see if Bio 30 and otherCAPE-rich propolis are useful for the treatment of NF patients. Copyright © 2008 John Wiley & Sons, Ltd.