Artepillin C (ARC) in Brazilian Green Propolis Selectively Blocks Oncogenic PAK1 Signaling and Suppresses the Growth of NF Tumors in Mice
Shanta M. Messerli1†, Mok-Ryeon Ahn2†, Kazuhiro Kunimasa2, Miyako Yanagihara3, Tomoki Tatefuji3, Ken Hashimoto3, Victor Mautner4, Yoshihiro Uto5, Hitoshi Hori5, Shigenori Kumazawa2, Kazuhiko Kaji2, Toshiro Ohta2 and Hiroshi Maruta4*
1Marine Biological Laboratory, Woods Hole, USA
2University of Shizuoka, Shizuoka, Japan
3Yamada Apiculture Center, Okayama, Japan
4University Hospital Uppendorf (UKE), Hamburg, Germany 5University of Tokushima, Tokushima, Japan
There are mainly three types of propolis whose major anticancer ingredients are entirely different: (1) CAPE (caffeic acid phenethyl ester)-based propolis in Europe, Far East and New Zealand, (2) artepillin C (ARC)-based Brazilian green propolis and (3) Brazilian red propolis. It was shown previously that NF (neurofibromatosis)- associated tumors require the kinase PAK1 for their growth, and CAPE-based propolis extracts such as Bio 30 suppress completely the growth of NF tumors in vivo by blocking PAK1 signaling. Also it was demon- strated that ARC suppresses angiogenesis, suggesting the possibility that ARC also blocks oncogenic PAK1 signaling. Here it is shown for the first time that both ARC and green propolis extract (GPE) indeed block the PAK1 signaling selectively, without affecting another kinase known as AKT. Furthermore, it was confirmed that ARC as well as GPE suppress almost completely the growth of human NF tumor xenografts in mice, as does Bio 30. These results suggest that both CAPE-based and ARC-based propolis extracts are natural anti- PAK1 remedies and could be among the first effective NF therapeutics available on the market. Since more than 70% of human cancers such as breast and prostate cancers require the kinase PAK1 for their growth, it is quite possible that GPE could be potentially useful for the treatment of these cancers, as is Bio 30.
* THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION. THIS IS NOT INTENDED TO DIAGNOSE, TREAT CURE OR PREVENT ANY DISEASE.