Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells.
10.4062/biomolther.2015.166
- Author:
Nak Yoon SUNG
1
;
Seung Cheol KIM
;
Yun Hwan KIM
;
Gihyeon KIM
;
Yunmi LEE
;
Gi Ho SUNG
;
Ji Hye KIM
;
Woo Seok YANG
;
Mi Seon KIM
;
Kwang Soo BAEK
;
Jong Hoon KIM
;
Jae Youl CHO
Author Information
1. Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. jaecho@skku.edu
- Publication Type:Original Article
- Keywords:
4-methyl-2,6-bis(1-phenylethyl)phenol;
Apoptotis;
Anti-cancer activity;
Cordyceps Bassiana
- MeSH:
Apoptosis;
Caspase 3;
Caspase 9;
Cell Line;
Cell Proliferation;
Cell Survival;
Chromatin;
Cordyceps;
Extracellular Vesicles;
Glioma;
Methods;
Phosphorylation
- From:Biomolecules & Therapeutics
2016;24(4):402-409
- CountryRepublic of Korea
- Language:English
-
Abstract:
It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.
