Mechanisms for the Magnolol-Induced Cell Death of Cgth W-2 Thyroid Carcinoma Cells
Resource
JOURNAL OF CELLULAR BIOCHEMISTRY v.101 n.4 pp.1011-1022
Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Journal Volume
v.101
Journal Issue
n.4
Pages
1011-1022
Date Issued
2007
Date
2007
Author(s)
HUANG, SHIH-HORNG
CHEN, YING
Abstract
Magnolol, a substance purified from the bark of Magnolia officialis, inhibits cell proliferation and induces apoptosis in a variety of cancer cells. The aim of this study was to study the effects of magnolol on CGTH W-2 thyroid carcinoma cells. After 24 h treatment with 80 然magnolol in serum-containing medium, about 50% of the cells exhibited apoptotic features and 20% necrotic features. Cytochrome-c staining was diffused in the cytoplasm of the apoptotic cells, but restricted to the mitochondria in control cells. Western blot analyses showed an increase in levels of activated caspases (caspase-3 and -7) and of cleaved poly (ADP-ribose) polymerase (PARP) by magnolol. Concomitantly, immunostaining for apoptosis inducing factor( AIF) showed a time-dependent translocation from the mitochondria to the nucleus. Inhibition of either PARP or caspase activity blocked magnolol-induced apoptosis, supporting the involvement of the caspases and PARP. In addition, magnolol activated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and inactivated Akt by decreasing levels of phosphorylated PTEN and phosphorylated Akt. These data suggest that magnolol promoted apoptosis probably by alleviating the inhibitory effect of Akt on caspase 9. Furthermore, inhibition of PARP activity, but not of caspase activity, completely prevented magnolol-induced necrosis, suggesting the notion that it might be caused by depletion of intracellular ATP levels due to PARP activation . These results show that magnolol initiates apoptosis via the cytochrome-c/caspase 3/PARP/AIF and PTEN/Akt/caspase 9/ PARP pathways and necrosis via PARP activation.
Subjects
MAGNOLOL
THYROID CARCINOMA CELLS
APOPTOSIS
NECROSIS
SIGNALING MECHANISM
SDGs
Type
journal article