SBF-1 almost completely blocked the activation of AR and
its subsequent signaling by DHT
It is known that activation of IGF-1 through glucose uptake will cause
the activation of AKT-FOXO1 axis (Iwamura, Sluss, Casamento & Cockett,
1993; McKeehan, Adams & Rosser, 1984). When the prostate cancer cells
were treated with 20 mM Glucose, 200 nM SBF-1 and 5 nM DHT or both SBF-1
and DHT for 3 h, SBF-1 decreased the protein levels of IGF-1, PCNA,
pAKTS473 and pFOXO1 in the presence of Glucose or DHT
(Fig. 5A and B), as well as the mRNA level of IGF-1 increased by DHT and
glucose (Fig. 5C). In Fig. 5D and E, we silenced the IGF-1 and FOXO1,
respectively in both LNCaP and PC3/AR+ cells. SBF-1
and DHT showed an opposite effect on the expressions of the downstream
signal proteins PCNA and Bcl-2. When they were used together, SBF-1
almost completely blocked the DTH-increased expressions of PCNA and
Bcl-2. These results suggest that SBF-1 may display its anti-PCa
activity despite the endogenous levels of androgens and AR mutation.