TY - JOUR
T1 - Anti-proliferative and pro-apoptotic activities of 4-methyl-2,6-bis(1-phenylethyl)phenol in cancer cells
AU - Sung, Nak Yoon
AU - Kim, Seung Cheol
AU - Kim, Yun Hwan
AU - Kim, Gihyeon
AU - Lee, Yunmi
AU - Sung, Gi Ho
AU - Kim, Ji Hye
AU - Yang, Woo Seok
AU - Kim, Mi Seon
AU - Baek, Kwang Soo
AU - Kim, Jong Hoon
AU - Cho, Jae Youl
N1 - Publisher Copyright:
© 2016 The Korean Society of Applied Pharmacology.
PY - 2016/7
Y1 - 2016/7
N2 - 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.
AB - 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.
KW - 4-methyl-2,6-bis(1-phenylethyl)phenol
KW - Anti-cancer activity
KW - Apoptotis
KW - Cordyceps bassiana
UR - http://www.scopus.com/inward/record.url?scp=84977473029&partnerID=8YFLogxK
U2 - 10.4062/biomolther.2015.166
DO - 10.4062/biomolther.2015.166
M3 - Article
AN - SCOPUS:84977473029
SN - 1976-9148
VL - 24
SP - 402
EP - 409
JO - Biomolecules and Therapeutics
JF - Biomolecules and Therapeutics
IS - 4
ER -