Morusin induces apoptosis and suppresses NF-kappaB activity in human colorectal cancer HT-29 cells.
Morusin is a pure compound isolated from root bark of Morusaustralis (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-G(1) phase, fragmentation of DNA, and condensation of chromatin. Morusin also inhibited the phosphorylation of IKK-alpha, IKK-beta and IkappaB-alpha, increased expression of IkappaB-alpha, and suppressed nuclear translocation of NF-kappaB and its DNA binding activity. Dephosphorylation of NF-kappaB 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-kappaB.
Lee
Jenq-Chang
JC
Department of Surgery, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Won
Shen-Jeu
SJ
Chao
Chien-Lin
CL
Wu
Feng-Ling
FL
Liu
Hsiao-Sheng
HS
Ling
Pin
P
Lin
Chun-Nan
CN
Su
Chun-Li
CL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D005419:Flavonoids; D016328:NF-kappa B; C057451:morusin; D020169:Caspases