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http://dx.doi.org/10.4062/biomolther.2015.166

Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells  

Sung, Nak Yoon (Department of Genetic Engineering, Sungkyunkwan University)
Kim, Seung Cheol (Division of Gynecologic Oncology Department of Obstetrics and Gynecology, Ewha Womans University Mokdong Hospital College of Medicine, Ewha Womans University)
Kim, Yun Hwan (Division of Gynecologic Oncology Department of Obstetrics and Gynecology, Ewha Womans University Mokdong Hospital College of Medicine, Ewha Womans University)
Kim, Gihyeon (Department of Chemistry, Kwangwoon University)
Lee, Yunmi (Department of Chemistry, Kwangwoon University)
Sung, Gi-Ho (Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University)
Kim, Ji Hye (Department of Genetic Engineering, Sungkyunkwan University)
Yang, Woo Seok (Department of Genetic Engineering, Sungkyunkwan University)
Kim, Mi Seon (Department of Genetic Engineering, Sungkyunkwan University)
Baek, Kwang-Soo (Department of Genetic Engineering, Sungkyunkwan University)
Kim, Jong-Hoon (Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University)
Cho, Jae Youl (Department of Genetic Engineering, Sungkyunkwan University)
Publication Information
Biomolecules & Therapeutics / v.24, no.4, 2016 , pp. 402-409 More about this Journal
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.
Keywords
4-methyl-2,6-bis(1-phenylethyl)phenol; Apoptotis; Anti-cancer activity; Cordyceps Bassiana;
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Times Cited By KSCI : 8  (Citation Analysis)
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