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

Sung NY, Kim SC, Kim YH, Kim G, Lee Y, Sung GH, Kim JH, Yang WS, Kim MS, Baek KS, Kim JH, Cho JY - Biomol Ther (Seoul) (2016)

Bottom Line: 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.Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of KTH-13-Me and its analogs.
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f1-bt-24-402: Chemical structure of KTH-13-Me and its analogs.

Mentions: Previously, we reported that Cordyceps bassiana has various pharmacological activities, such as anti-inflammatory, anti-atopic dermatitis, and anti-cancer effects (Byeon et al., 2011a; Byeon et al., 2011b; Wu et al., 2011; Kim et al., 2015a). Moreover, 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), which displays anti-tumor activity through inducing apoptosis in various cancer cells (Kim et al., 2015a), was isolated from the butanol fraction of Cordyceps bassiana. Based on those results, we established total synthesis conditions to produce KTH-13, and further synthesized several compounds, including 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me), and analogs thereof with structural similarity to KTH-13 (Fig. 1). Since these compounds are expected to have anti-cancer activity, in this study we aimed to investigate the anti-proliferative activities as well as the molecular mechanisms of these compounds.


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

Sung NY, Kim SC, Kim YH, Kim G, Lee Y, Sung GH, Kim JH, Yang WS, Kim MS, Baek KS, Kim JH, Cho JY - Biomol Ther (Seoul) (2016)

Chemical structure of KTH-13-Me and its analogs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4930284&req=5

f1-bt-24-402: Chemical structure of KTH-13-Me and its analogs.
Mentions: Previously, we reported that Cordyceps bassiana has various pharmacological activities, such as anti-inflammatory, anti-atopic dermatitis, and anti-cancer effects (Byeon et al., 2011a; Byeon et al., 2011b; Wu et al., 2011; Kim et al., 2015a). Moreover, 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), which displays anti-tumor activity through inducing apoptosis in various cancer cells (Kim et al., 2015a), was isolated from the butanol fraction of Cordyceps bassiana. Based on those results, we established total synthesis conditions to produce KTH-13, and further synthesized several compounds, including 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me), and analogs thereof with structural similarity to KTH-13 (Fig. 1). Since these compounds are expected to have anti-cancer activity, in this study we aimed to investigate the anti-proliferative activities as well as the molecular mechanisms of these compounds.

Bottom Line: 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.Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus