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Biochem Biophys Res Commun. 2008 Jul 18;372(1):236-42. doi: 10.1016/j.bbrc.2008.05.023. Epub 2008 May 14.

Morusin induces apoptosis and suppresses NF-kappaB activity in human colorectal cancer HT-29 cells.

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1
Department of Surgery, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

Abstract

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.

PMID:
18485277
DOI:
10.1016/j.bbrc.2008.05.023
[Indexed for MEDLINE]
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