Frondoside A from Sea Cucumber and Nymphaeols from
Okinawa Propolis:
Natural anti-cancer agents that selectively inhibit PAK1 in vitro
Natural anti-cancer agents that selectively inhibit PAK1 in vitro
BC. Nguyen1, K. Yoshimura2, S. Kumazawa2, S. Tawata1, H. Maruta3,*
1PAK Research
Center, University of the Ryukyus, Okinawa 903-0213, Japan
2Dept of Food and Nutritional Sci,
University of Shizuoka, Shizuoka 422-8526, Japan
3PAK Research Center,
Melbourne, Australia 3055
ABSTRACT
A sulfated saponin
called “Frondoside A” (FRA) from sea cucumber and ingredients from Okinawa
propolis (OP) have been previously shown to suppress the PAK1-dependent growth
of A549 lung cancer as well as pancreatic cancer cells. However, the precise
molecular mechanism underlying their anti-cancer action still remains to be
clarified. In this study, for the first time, we found that both FRA and OP
directly inhibit PAK1 in vitro in a selective
manner (far more effectively than two other oncogenic kinases, LIMK and AKT).
Furthermore, at least two major anti-cancer ingredients of OP, Nymphaeols A and C, also directly inhibit PAK1 in vitro in a selective manner. To the best of our knowledge, FRA
is the first marine compound that selectively inhibits PAK1. Likewise, these Nymphaeols are the first propolis ingredients that selectively
inhibit PAK1.
Note: In an attempt to determine the specific role of geranyl side chains in either anti-cancer/cell-permeability or anti-PAK1 activity/kinase specificity if any, we are planning to study the potential anti-cancer and anti-PAK1 activity of far simpler flavonoids such as naringenin and sakuranetin which contain no geranyl side chain.
Table 1
Anti-cancer activity and anti-kinase specificity of
Frondoside A and Okinawa propolis (OP) ingredients (nymphaeols)
Anti-cancer
(IC50)
|
Anti-PAK1
(IC50)
|
Anti-LIMK
(IC50)
|
Anti-AKT
(IC50)
|
|
Frondoside A
|
0.6
|
1.2
|
60
|
59
|
Okinawa propolis
|
12
|
10
|
39
|
30
|
Nymphaeol A
|
3.6
|
9.6
|
161
|
42
|
Nymphaeol C
|
6.5
|
9.8
|
171
|
74
|
Curcumin
|
23
|
16
|
30
|
44
|
IC50 value is in μM, except forOkinawa
propolis (OP) in μg/mL.
Note: In an attempt to determine the specific role of geranyl side chains in either anti-cancer/cell-permeability or anti-PAK1 activity/kinase specificity if any, we are planning to study the potential anti-cancer and anti-PAK1 activity of far simpler flavonoids such as naringenin and sakuranetin which contain no geranyl side chain.
