title: 4-(Tert-butyl)-2,6-bis(1-phenylethyl)phenol induces pro-apoptotic activity.
abstract: Previously, we found that KTH-13 isolated from the butanol fraction of Cordyceps bassiana (Cb-BF) displayed anti-cancer activity. To improve its antiproliferative activity and production yield, we employed a total synthetic approach and derivatized KTH-13 to obtain chemical analogs. In this study, one KTH-13 derivative, 4-(tert-butyl)-2,6-bis(1-phenylethyl)phenol (KTH-13-t-Bu), was selected to test its anti-cancer activity. KTH-13-t-Bu diminished the proliferation of C6 glioma, MDA-MB-231, LoVo, and HCT-15 cells. KTH-13-t-Bu induced morphological changes in C6 glioma cells in a dose-dependent manner. KTH-13-t-Bu also increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, KTH-13-t-Bu increased the levels of cleaved caspase-3 and -9. In contrast, KTH-13-t-Bu upregulated the levels of pro- and cleaved forms of caspase-3, -8, and -9 and Bcl-2. Phospho-STAT3, phospho-Src, and phospho-AKT levels were also diminished by KTH13-t-Bu treatment. Therefore, these results strongly suggest that KTH-13-t-Bu can be considered a novel anti-cancer drug displaying pro-apoptotic activity.
authors.affiliation: Depatment of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Kwangwoon University, Seoul 01897, Korea.
authors.forename: Yunmi
authors.initials: Y
authors.lastname: Lee
authors.affiliation: School of Systems Biomedical Science, Soongsil University, Seoul 06978, Korea.
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Depatment of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
keywords: Anti-cancer activity; KTH-13-t-Bu; Pro-apoptotic activity; STAT-3; Src