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

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

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91 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume372
Issue number1
DOIs
Publication statusPublished - 2008 Jul 18

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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