My watch list
my.bionity.com  
Login  

Marine Drugs, Vol. 16, Pages 212: Breaking down Leukemia Walls: Heteronemin, a Sesterterpene Derivative, Induces Apoptosis in Leukemia Molt4 Cells through Oxidative Stress, Mitochondrial Dysfunction and Induction of Talin Expression

Marine Drugs, Vol. 16, Pages 212: Breaking down Leukemia Walls: Heteronemin, a Sesterterpene Derivative, Induces Apoptosis in Leukemia Molt4 Cells through Oxidative Stress, Mitochondrial Dysfunction and Induction of Talin Expression

Marine Drugs doi: 10.3390/md16060212

Authors: Yu-Cheng Chen Mei-Chin Lu Mohamed El-Shazly Kuei-Hung Lai Tung-Ying Wu Yu-Ming Hsu Yi-Lun Lee Yi-Chang Liu

Heteronemin, the most abundant secondary metabolite in the sponge Hippospongia sp., exhibited potent cytotoxic activity against several cancer cell lines. It increased the percentage of apoptotic cells and reactive oxygen species (ROS) in Molt4 cells. The use of ROS scavenger, N-acetyl cysteine (NAC), suppressed both the production of ROS from mitochondria and cell apoptosis that were induced by heteronemin treatment. Heteronemin upregulated talin and phosphorylated talin expression in Molt4 cells but it only upregulated the expression of phosphorylated talin in HEK293 cells. However, pretreatment with NAC reversed these effects. Talin siRNA reversed the activation of pro-apoptotic cleaved caspases 3 and 9. On the other hand, the downstream proteins including FAK and NF-κB (p65) were not affected. In addition, we confirmed that heteronemin directly modulated phosphorylated talin expression through ROS generation resulting in cell apoptosis, but it did not affect talin/FAK complex. Furthermore, heteronemin interfered with actin microfilament and caused morphology changes. Taken together, these findings suggest that the cytotoxic effect of heteronemin is associated with oxidative stress and induction of phosphorylated talin expression. Our results suggest that heteronemin represents an interesting candidate which can be further developed as a drug lead against leukemia.

Authors:   Chen, Yu-Cheng ; Lu, Mei-Chin ; El-Shazly, Mohamed ; Lai, Kuei-Hung ; Wu, Tung-Ying ; Hsu, Yu-Ming ; Lee, Yi-Lun ; Liu, Yi-Chang
Journal:   Marine Drugs
Volume:   16
edition:   6
Year:   2018
Pages:   212
DOI:   10.3390/md16060212
Publication date:   17-Jun-2018
Facts, background information, dossiers
More about Molecular Diversity Preservation International
Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE