Characterization of oleanolic acid derivative for colon cancer targeting with positron emission tomography.
Oleanolic acid (OA) is a pentacyclic triterpenoid found in various plant species. Triterpenoid compounds have been shown to inhibit tumor proliferation and to induce apoptosis in cancer cells. We synthesized an OA derivative and evaluated its inhibitory effects on cell proliferation in human colon cancer. Radioisotope-labeled OA was prepared for noninvasive monitoring of tumor progression in vitro and in vivo. The OA derivative decreased cell survival in a concentration-dependent manner and increased apoptosis in HT-29 cells. Furthermore, it induced downregulation of cyclin D1, Cox-2, Bcl-2 and Bcl-xL mRNA expression and upregulation of the mRNA expression of the anti-apoptotic Bax protein in HT29 cells. NF-κB p65 and IκB expression also decreased, whereas expression of the apoptosis marker, the cleaved form of PARP-1, significantly increased in OA derivative-treated HT-29 cells. Radioisotope-labeled OA (68Ga-NOTA-OA) showed significantly high tumor uptake, as assessed by biodistribution and positron emission tomography imaging analyses, at 1 h post-injection in the human colon cancer xenograft model. Our results demonstrate that the OA derivative has promising properties as an anticancer drug and as an imaging tool for tumor targeting.
a Magnetic Resonance Research Center, Korea Basic Science Institute (KBSI) Chungbuk Republic of Korea.
Sung-Min
SM
Kim
a Magnetic Resonance Research Center, Korea Basic Science Institute (KBSI) Chungbuk Republic of Korea.
Il Ha
IH
Jeong
a Magnetic Resonance Research Center, Korea Basic Science Institute (KBSI) Chungbuk Republic of Korea.
Min Su
MS
Yim
a Magnetic Resonance Research Center, Korea Basic Science Institute (KBSI) Chungbuk Republic of Korea.
Min Kyung
MK
Chae
a Magnetic Resonance Research Center, Korea Basic Science Institute (KBSI) Chungbuk Republic of Korea.
Hak Nam
HN
Kim
b Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF) Daegu Republic of Korea.
Dong Kue
DK
Kim
c Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul Republic of Korea.
Choong Mo
CM
Kang
c Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul Republic of Korea.
Yearn Seong
YS
Choe
a Magnetic Resonance Research Center, Korea Basic Science Institute (KBSI) Chungbuk Republic of Korea.
Chulhyun
C
Lee
a Magnetic Resonance Research Center, Korea Basic Science Institute (KBSI) Chungbuk Republic of Korea.
Eun Kyoung
EK
Ryu
Anticancer drug; apoptosis; cancer targeting; colon cancer; oleanolic acid derivative; positron emission tomography