Morusin induces apoptosis and suppresses NF-{kappa}B activity in human colorectal cancer HT-29 cells
- Department of Surgery, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)
- Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China)
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{sub 1} phase, fragmentation of DNA, and condensation of chromatin. Morusin also inhibited the phosphorylation of IKK-{alpha}, IKK-{beta} and I{kappa}B-{alpha}, increased expression of I{kappa}B-{alpha}, and suppressed nuclear translocation of NF-{kappa}B and its DNA binding activity. Dephosphorylation of NF-{kappa}B 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-{kappa}B.
- OSTI ID:
- 21143776
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 372; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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