TY - JOUR
T1 - Selective inhibition of human type-5 17 beta-hydroxysteroid dehydrogenase (AKR1C3) by baccharin, a component of Brazilian propolis
AU - Endo, Satoshi
AU - Matsunaga, Toshiyuki
AU - Kanamori, Ayano
AU - Otsuji, Yoko
AU - Nagai, Hiroko
AU - Sundaram, Krithika
AU - El-Kabbani, Ossama
AU - Toyooka, Naoki
AU - Ohta, Shozo
AU - Hara, Akira
PY - 2012
Y1 - 2012
N2 - The human aldo-keto reductase (AKR) 1C3, also known as type-5, 17 beta-hydrogenase and prostaglandin F-synthase has been suggested as a therapeutic target in the treatment of prostate and breast cancers.In this study,AKR1C3 inhibition was examined by Brazilian proplis-derived cinnamic acid derivatives that show potential antitumor activity, and it was found that baccharin (1) is a potent competitive inhibitor (K(i)56nM) with high selectivity ,showing no significant inhibition toward other AKR1C isoforms site-directed mutagenesis studies suggested that the non-conserved residues Ser118,Met120, and Phe311 in AKR1C3 are important for determining the inhibitory potency and selectivity of 1. The AKR1C3 mediated of 17 ketosterol and farnesal in cancer cells was inhibited by 1,which was effectively from 0.2 mu M with an IC50 value of about 30 mu M. Additionally 1 suppressed the proliferation of PC3 prostatic cancer cells stimulated by AKR1C3 overexpression. This study is the first demonstration that 1 is a highly selective inhibitor of AKR1C3.
AB - The human aldo-keto reductase (AKR) 1C3, also known as type-5, 17 beta-hydrogenase and prostaglandin F-synthase has been suggested as a therapeutic target in the treatment of prostate and breast cancers.In this study,AKR1C3 inhibition was examined by Brazilian proplis-derived cinnamic acid derivatives that show potential antitumor activity, and it was found that baccharin (1) is a potent competitive inhibitor (K(i)56nM) with high selectivity ,showing no significant inhibition toward other AKR1C isoforms site-directed mutagenesis studies suggested that the non-conserved residues Ser118,Met120, and Phe311 in AKR1C3 are important for determining the inhibitory potency and selectivity of 1. The AKR1C3 mediated of 17 ketosterol and farnesal in cancer cells was inhibited by 1,which was effectively from 0.2 mu M with an IC50 value of about 30 mu M. Additionally 1 suppressed the proliferation of PC3 prostatic cancer cells stimulated by AKR1C3 overexpression. This study is the first demonstration that 1 is a highly selective inhibitor of AKR1C3.
UR - http://pubs.acs.org/journal/jnprdf
U2 - 10.1021/np201002x
DO - 10.1021/np201002x
M3 - Article
SN - 0163-3864
VL - 75
SP - 716
EP - 721
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 4
ER -
