Artepillin C (ARC) in Brazilian green propolis selectively blocks oncogenic PAK1 signaling and suppresses the growth of NF tumors in mice

Phytotherapy Research

Volumn 23, Issue 3, 2009, Pages 423-427

  Messerli, Shanta M ^a   Ahn, Mok Ryeon ^b   Kunimasa, Kazuhiro ^b   Yanagihara, Miyako ^c   Tatefuji, Tomoki ^c   Hashimoto, Ken ^c   Mautner, Victor ^d   Uto, Yoshihiro ^e   Hori, Hitoshi ^e   Kumazawa, Shigenori ^b   Kaji, Kazuhiko ^b   Ohta, Toshiro ^b   Maruta, Hiroshi ^d,e  

^a MARINE BIOLOGICAL LABORATORY   (United States)

^b UNIVERSITY OF SHIZUOKA   (Japan)

^c Yamada Apiculture Center Inc   (Japan)

^d UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^e UNIVERSITY OF TOKUSHIMA   (Japan)

Author keywords

Artepillin c; Brazilian green propolis; Neurofibromatosis; NF; PAK1

Indexed keywords

ARTEPILLIN C; BIO 30; CAFFEIC ACID PHENETHYL ESTER; GREEN PROPOLIS EXTRACT; P21 ACTIVATED KINASE 1; PROPOLIS; PROTEIN KINASE B; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; FEMALE; HUMAN; HUMAN CELL; MOUSE; NEUROFIBROMATOSIS; NONHUMAN; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS; CAFFEIC ACIDS; CELL LINE, TUMOR; FEMALE; MICE; MICE, NUDE; NEOPLASMS, EXPERIMENTAL; NEUROFIBROMATOSES; P21-ACTIVATED KINASES; PHENYLETHYL ALCOHOL; PHENYLPROPIONATES; PROPOLIS; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

MUS;

EID: 61449164799     PISSN: 0951418X     EISSN: 10991573     Source Type: Journal    
DOI: 10.1002/ptr.2658     Document Type: Article

References (26)

1. Ahn MR, Kunimasa K, Ohta T et al. 2007. Suppression of tumor-induced angiogenesis by Brazilian green propolis: major component artepillin C inhibits in vitro tube formation and endothelial cell proliferation. Cancer Lett 252: 235-243.
2. Awale S, Li F, Onozuka H et al. 2008. Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient- deprived condition. Bioorg Med Chem 16: 181-189.
3. Bagheri-Yarmand R, Mazumdar A, Sahin AA. 2006. LIM kinase 1 increases tumor metastasis of human breast cancer cells via regulation of the urokinase-type plasminogen activator system. Int J Cancer 118: 2703-2710.
4. Bos JL. 1989. RAS oncogenes in human cancer: A review. Cancer Res 49: 4682-4689.
5. Demestre M, Messerli S, Celli N et al. 2008. CAPE (Caffeic acid phenethyl ester)-based propolis extract (Bio 30) suppresses the growth of human neurofibromatosis (NF) tumor xeno- grafts in mice. Phytother Res 22: in press.
6. He H, Hirokawa Y, Gazit A et al. 2004. The Tyr-kinase inhibitor AG 879, that blocks the ETK-PAK1 interaction, suppresses the RAS-induced PAK1 activation and malignant transformation. Cancer Biol Ther 3: 96-101.
7. He H, Hirokawa Y, Manser E et al. 2001. Signal therapy of RAS induced cancers in combination of AG 879 and PP1, specific inhibitors for ErbB2 and Src family kinases, that block PAK activation. Cancer J 7: 191-202.
8. Hirokawa Y, Arnold M, Nakajima H et al. 2005b. Signal therapy of breast cancer xenograft in mice by the HDAC inhibitor FK228 that blocks the activation of PAK1 and abrogates the tamoxifen-resistance. Cancer Biol Ther 4: 956-960.
9. Hirokawa Y, Levitzki A, Lessene G et al. 2007. Signal therapy of human pancreatic cancer and NF1-deficient breast cancer xenograft in mice by a combination of PP1 and GL-2003, anti-PAK1 drugs (Tyr-kinase inhibitors). Cancer Lett 245: 242-251.
10. Hirokawa Y, Nakajima H, Hanemann O et al. 2005a. Signal therapy of Nf1-deficient tumor xenograft in mice. Cancer Biol Ther 4: 379-381.
11. Hirokawa Y, Nheu T, Grimm K et al. 2006. Sichuan pepper extracts block the PAK1/cyclin D1 pathway and the growth of NF1-deficient cancer xenograft in mice. Cancer Biol Ther 5: 305-309.
12. Hirokawa Y, Tikoo A, Huynh J et al. 2004. A clue to the therapy of neurofibromatosis type 2: NF2/merlin is a PAK1 inhibitor. Cancer J 10: 20-26.
13. Kiosses WB, Hood J, Yang S et al. 2002. A dominant-negative p65 PAK peptide inhibits angiogenesis. Circ Res 90: 697-702.
14. Lepont P, Stickney JT, Foster LA et al. 2008. Point mutation in the NF2 gene of HEI-193 human Schwannoma cells results in the expression of a merlin isoform with attenuated growth suppressive activity. Mutat Res 637: 142-151.
15. Levitzki A, Gazit A. 1995. Tyrosine kinase inhibition: an approach to drug development. Science 267: 1782-1788.
16. Maruta H, Ohta T. 2008. Signal therapy: propolis and pepper extracts as cancer therapeutics. In Complementary and Alternative Therapies and the Aging Population, Watson RR (ed.). Elsevier, Inc: San Diego.
17. Mosmann T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63.
18. Nheu T, He H, Hirokawa Y et al. 2002. The K252a derivatives, inhibitors for the PAK/MLK kinase family, selectively block the growth of RAS transformants. Cancer J 8: 328-335.
19. Prabhakar S, Messerli S, Stemmer-Rachamimov A et al. 2007. Treatment of implantable NF2 Schwannoma tumor models with oncolytic herpes simplex virus G47 Delta. Cancer Gene Ther 14: 460-467.
20. Shimizu K, Das SK, Baba M et al. 2006. Dietary artepillin C suppresses the formation of aberrant crypt foci induced by azoxymethane in mouse colon. Cancer Lett 240: 135-142.
21. Stockton R, Schaefer E, Schwartz M. 2004. p21-activated kinase regulates endothelial permeability through modulation of contractility. J Biol Chem 279: 46621-46630.
22. Stopera SA, Murphy LC, Bird RP. 1992. Evidence for a ras gene mutation in azoxymethane-induced colonic aberrant crypts in Sprague-Dawley rats: earliest recognizable precursor lesions of experimental colon cancer. Carcinogenesis 13:2081-2085.
23. Tran NH, Frost JA. 2003. Phosphorylation of Raf-1 by p21- activated kinase 1 and Src regulates Raf-1 autoinhibition. J Biol Chem 278: 11221-11226.
24. Uto Y, Hirata A, Fujita T et al. 2002. First total synthesis of artepillin C established by o,o'-diprenylation of p-halophenols in water. J Org Chem 67: 2355-2357.
25. Vadlamudi RK, Kumar R. 2003. p21-activated kinases in human cancer. Cancer Metastasis Rev 22: 385-393.
26. Zenke FT, King CC, Bohl BP et al. 1999. Identification of a central phosphorylation site in p21-activated kinase regulating autoinhibition and kinase activity. J Biol Chem 274: 32565-32573.