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Abstract Title:

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

Abstract Source:

Biochem Biophys Res Commun. 2008 Jul 18 ;372(1):236-42. Epub 2008 May 14. PMID: 18485277

Abstract Author(s):

Jenq-Chang Lee, Shen-Jeu Won, Chien-Lin Chao, Feng-Ling Wu, Hsiao-Sheng Liu, Pin Ling, Chun-Nan Lin, Chun-Li Su

Article Affiliation:

Jenq-Chang Lee

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.

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