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

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

  • Biochem Biophys Res Commun. 2008 Jul 18;372(1):236-42. doi: 10.1016/j.bbrc.2008.05.023.
Jenq-Chang Lee 1 Shen-Jeu Won Chien-Lin Chao Feng-Ling Wu Hsiao-Sheng Liu Pin Ling Chun-Nan Lin Chun-Li Su
Affiliations

Affiliation

  • 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.

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