Unknown

Dataset Information

0

(3-Chloroacetyl)-indole, a novel allosteric AKT inhibitor, suppresses colon cancer growth in vitro and in vivo.


ABSTRACT: Indole-3-carbinol (I3C) is produced in Brassica vegetables such as broccoli and cabbage and has been shown to inhibit proliferation and induce apoptosis in various cancer cells, including breast, prostate, colon, and leukemia. However, only high doses of I3C were shown to inhibit cell proliferation (IC(50) = 200-300 ?mol/L). Our goal here was to develop a more potent antitumor agent by modifying the structure of I3C. We created I3C derivatives and found that (3-chloroacetyl)-indole (3CAI) more strongly inhibited colon cancer cell growth than I3C. In addition, by screening 85 kinases in a competitive kinase assay, we found that 3CAI was a specific AKT inhibitor. AKT is a serine/threonine kinase that plays a pivotal role in promoting transformation and chemoresistance by inducing proliferation and inhibiting apoptosis. Therefore, AKT is regarded as a critical target for cancer therapy. 3ICA, a derivative of I3C, is a potent and specific AKT inhibitor. This compound showed significant inhibition of AKT in an in vitro kinase assay and suppressed expression of AKT direct downstream targets such as mTOR and GSK3? as well as induced growth inhibition and apoptosis in colon cancer cells. In addition, oral administration of this potent AKT inhibitor suppressed cancer cell growth in an in vivo xenograft mouse model.

SUBMITTER: Kim DJ 

PROVIDER: S-EPMC3244047 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

(3-Chloroacetyl)-indole, a novel allosteric AKT inhibitor, suppresses colon cancer growth in vitro and in vivo.

Kim Dong Joon DJ   Reddy Kanamata K   Kim Myoung Ok MO   Li Yan Y   Nadas Janos J   Cho Yong-Yeon YY   Kim Jong-Eun JE   Shim Jung-Hyun JH   Song Nu Ry NR   Carper Andria A   Lubet Ronald A RA   Bode Ann M AM   Dong Zigang Z  

Cancer prevention research (Philadelphia, Pa.) 20110901 11


Indole-3-carbinol (I3C) is produced in Brassica vegetables such as broccoli and cabbage and has been shown to inhibit proliferation and induce apoptosis in various cancer cells, including breast, prostate, colon, and leukemia. However, only high doses of I3C were shown to inhibit cell proliferation (IC(50) = 200-300 μmol/L). Our goal here was to develop a more potent antitumor agent by modifying the structure of I3C. We created I3C derivatives and found that (3-chloroacetyl)-indole (3CAI) more s  ...[more]

Similar Datasets

| S-EPMC3643416 | biostudies-literature
| S-EPMC8072828 | biostudies-literature
| S-EPMC2987445 | biostudies-literature
| S-EPMC2879416 | biostudies-literature
2021-05-05 | GSE163790 | GEO
2021-05-05 | GSE163592 | GEO
2021-05-05 | GSE163599 | GEO
| S-EPMC8085867 | biostudies-literature
2021-05-05 | GSE163789 | GEO
2021-05-05 | GSE163786 | GEO