title: Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells.
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.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Nak Yoon
authors.initials: NY
authors.lastname: Sung
authors.affiliation: Division of Gynecologic Oncology Department of Obstetrics and Gynecology, Ewha Womans University Mokdong Hospital College of Medicine, Ewha Womans University, Seoul 03760, Republic of Korea.
authors.forename: Seung Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Division of Gynecologic Oncology Department of Obstetrics and Gynecology, Ewha Womans University Mokdong Hospital College of Medicine, Ewha Womans University, Seoul 03760, Republic of Korea.
authors.forename: Yun Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Kwangwoon University, Seoul 01897, Republic of Korea.
authors.forename: Gihyeon
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Kwangwoon University, Seoul 01897, Republic of Korea.
authors.forename: Yunmi
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Institute for Bio-Medical Convergence, International St. Mary's Hospital and College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea.
authors.forename: Gi-Ho
authors.initials: GH
authors.lastname: Sung
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Yang
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Mi Seon
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Baek
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
keywords: 4-methyl-2; 6-bis(1-phenylethyl)phenol; Anti-cancer activity; Apoptotis; Cordyceps Bassiana