ARC (artepillin C) in Propolis: not only "Anti-cancer", but also "Anti-diabetic"

Brazilian green propolis extract (GPE) contains the anti-cancer ingredient
"ARC" (artepillin C) which we found a few years ago selectively blocks the
oncogenic kinase "PAK1", without affecting another oncogenic kinase AKT.
GPE has been used for the therapy of PAK1-dependent solid tumors which represent
more than 70% of all human cancers, since its anti-cancer property was found
two decades ago. Interestingly, however, GPE was often used for the therapy
of insulin-resistant diabetes (type 2) as well, although the anti-diabetic
ingredient in GPE has not been identified until recently.

This year Je-Tae Woo's group at Chubu University in Japan found that ARC
is a ligand for the nuclear receptor "PPAR gamma" which boosts the cellular
glucose uptake from blood stream by up-regulating the glucose transporter
"GLUT-4" (1).

Just like ARC, CAPE (caffeic acid phenethyl ester), the major anti-cancer
ingredient in NZ propolis such as "Bio 30" not only blocks selectively PAK1,
but also activates a tumor suppressive kinase called "AMPK". AMPK then activates
GLUT-4, boosting the cellular glucose uptake. Thus, CAPE-based propolis
is also useful for not only for cancer therapy, but also for the treatment
of diabetes (type 2).

Interestingly, another natural compound called "emodin" also shares both
anti-cancer and anti-diabetic properties with ARC and CAPE. This anthroquinone
derivative blocks PAK1, suppressing the growth of cancers, and activates
both AMPK and PPAR gamma, boosting the cellular glucose uptake. Thus, in
principle, emodin-rich Chinese herb called "Da Huang" (big yellow) root
extract would be useful for both cancer and diabetes therapies. Amazingly,
at least a dozen other natural compounds such as curcumin, resveratrol,
apigenin, berberine, capsaicin/capsiate, and salidroside are known to share
the same anti-cancer/anti-diabetic property with ARC, CAPE and emodin, both
blocking PAK1 and activating GLUT-4.

References:

1. Choi SS, Cha BY, Iida K, Lee YS, et al. Artepillin C, as a PPARgamma
ligand, enhances adipocyte differentiation and glucose uptake in 3T3-L1
cells. Biochem Pharmacol. 2011; 81: 925-33.