Abstract
Morusin is a pure compound isolated from root bark of Morus australis (Moraceae). In this study, we demonstrated that morusin significantly inhibited the growth and clonogenicity of human colorectal cancer HT-29 cells. Apoptosis induced by morusin was characterized by accumulation of cells at the sub-G1 phase, fragmentation of DNA, and condensation of chromatin. Morusin also inhibited the phosphorylation of IKK-α, IKK-β and IκB-α, increased expression of IκB-α, and suppressed nuclear translocation of NF-κB and its DNA binding activity. Dephosphorylation of NF-κB upstream regulators PI3K, Akt and PDK1 was also displayed. In addition, activation of caspase-8, change of mitochondrial membrane potential, release of cytochrome c and Smac/DIABLO, and activation of caspase-9 and -3 were observed at the early time point. Downregulation in the expression of Ku70 and XIAP was exhibited afterward. Caspase-8 or wide-ranging caspase inhibitor suppressed morusin-induced apoptosis. Therefore, the antitumor mechanism of morusin in HT-29 cells may be via activation of caspases and inhibition of NF-κB.
| Original language | English |
|---|---|
| Pages (from-to) | 236-242 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 372 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2008 Jul 18 |
Fingerprint
Keywords
- Apoptosis
- Caspases
- Colorectal cancer
- Morusin
- NF-κB
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Morusin induces apoptosis and suppresses NF-κB activity in human colorectal cancer HT-29 cells. / Lee, Jenq Chang; Won, Shen Jeu; Chao, Chien Lin; Wu, Feng Ling; Liu, Hsiao Sheng; Ling, Pin; Lin, Chun Nan; Su, Chun-Li.
In: Biochemical and Biophysical Research Communications, Vol. 372, No. 1, 18.07.2008, p. 236-242.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Morusin induces apoptosis and suppresses NF-κB activity in human colorectal cancer HT-29 cells
AU - Lee, Jenq Chang
AU - Won, Shen Jeu
AU - Chao, Chien Lin
AU - Wu, Feng Ling
AU - Liu, Hsiao Sheng
AU - Ling, Pin
AU - Lin, Chun Nan
AU - Su, Chun-Li
PY - 2008/7/18
Y1 - 2008/7/18
N2 - Morusin is a pure compound isolated from root bark of Morus australis (Moraceae). In this study, we demonstrated that morusin significantly inhibited the growth and clonogenicity of human colorectal cancer HT-29 cells. Apoptosis induced by morusin was characterized by accumulation of cells at the sub-G1 phase, fragmentation of DNA, and condensation of chromatin. Morusin also inhibited the phosphorylation of IKK-α, IKK-β and IκB-α, increased expression of IκB-α, and suppressed nuclear translocation of NF-κB and its DNA binding activity. Dephosphorylation of NF-κB upstream regulators PI3K, Akt and PDK1 was also displayed. In addition, activation of caspase-8, change of mitochondrial membrane potential, release of cytochrome c and Smac/DIABLO, and activation of caspase-9 and -3 were observed at the early time point. Downregulation in the expression of Ku70 and XIAP was exhibited afterward. Caspase-8 or wide-ranging caspase inhibitor suppressed morusin-induced apoptosis. Therefore, the antitumor mechanism of morusin in HT-29 cells may be via activation of caspases and inhibition of NF-κB.
AB - Morusin is a pure compound isolated from root bark of Morus australis (Moraceae). In this study, we demonstrated that morusin significantly inhibited the growth and clonogenicity of human colorectal cancer HT-29 cells. Apoptosis induced by morusin was characterized by accumulation of cells at the sub-G1 phase, fragmentation of DNA, and condensation of chromatin. Morusin also inhibited the phosphorylation of IKK-α, IKK-β and IκB-α, increased expression of IκB-α, and suppressed nuclear translocation of NF-κB and its DNA binding activity. Dephosphorylation of NF-κB upstream regulators PI3K, Akt and PDK1 was also displayed. In addition, activation of caspase-8, change of mitochondrial membrane potential, release of cytochrome c and Smac/DIABLO, and activation of caspase-9 and -3 were observed at the early time point. Downregulation in the expression of Ku70 and XIAP was exhibited afterward. Caspase-8 or wide-ranging caspase inhibitor suppressed morusin-induced apoptosis. Therefore, the antitumor mechanism of morusin in HT-29 cells may be via activation of caspases and inhibition of NF-κB.
KW - Apoptosis
KW - Caspases
KW - Colorectal cancer
KW - Morusin
KW - NF-κB
UR - http://www.scopus.com/inward/record.url?scp=46549090195&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=46549090195&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.05.023
DO - 10.1016/j.bbrc.2008.05.023
M3 - Article
VL - 372
SP - 236
EP - 242
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -