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Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells
- Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells
- Sung, Nak Yoon; Kim, Seung Cheol; Kim, Yun Hwan; Kim, Gihyeon; Lee, Yunmi; Sung, Gi-Ho; Kim, Ji Hye; Yang, Woo Seok; Kim, Mi Seon; Baek, Kwang-Soo; Kim, Jong-Hoon; Choi, Jae Youl
- Ewha Authors
- 김승철; 김윤환
- SCOPUS Author ID
- 김승철; 김윤환
- Issue Date
- Journal Title
- BIOMOLECULES & THERAPEUTICS
- 1976-9148; 2005-4483
- vol. 24, no. 4, pp. 402 - 409
- 4-methyl-2,6-bis(1-phenylethyl)pbenol; Apoptotis; Anti-cancer activity; Cordyceps Bassiana
- KOREAN SOC APPLIED PHARMACOLOGY
- SCIE; SCOPUS; KCI
- 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 06. 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/Pl. 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.
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