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
N1 - Funding Information:
This study was supported by grants from the National Science Council, Taiwan, Republic of China (NSC 95-2313-B-309-001).
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.
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U2 - 10.1016/j.bbrc.2008.05.023
DO - 10.1016/j.bbrc.2008.05.023
M3 - Article
C2 - 18485277
AN - SCOPUS:46549090195
SN - 0006-291X
VL - 372
SP - 236
EP - 242
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
