Ji L, Shen K, Liu J, Chen Y, Liu T, Wang Z.
Key Laboratory of Standardization of Chinese Medicines of Ministry of
Education, Shanghai Key Laboratory of Complex Prescription, Institute
of Chinese Materia Medica, Shanghai University of Traditional Chinese
Medicine, Shanghai, People's Republic China. jll_syc@yahoo.com.cn
Andrographolide (ANDRO), a diterpenoid lactone isolated from the
traditional herbal plant Andrographis paniculata, was reported to
induce apoptosis in hepatoma Hep3B cells in our previous study (Ji LL,
Liu TY, Liu J, Chen Y, Wang ZT. Andrographolide inhibits human
hepatoma-derived Hep3B cells growth through the activation of c-Jun
N-terminal kinase. Planta Med 2007; 73: 1397-1401). The present
investigation was carried out to observe whether cellular reduced
glutathione (GSH) plays important roles in ANDRO-induced apoptosis.
ANDRO initially increased intracellular GSH levels which then
decreased later, while inhibition of cellular GSH synthesis by
L-Buthionine-(S,R)-sulfoximine (BSO) augmented ANDRO-induced
cytotoxicity and apoptosis in Hep3B cells. On the other hand, the
thiol antioxidant dithiothreitol (DTT) rescued ANDRO-depleted cellular
GSH, and abrogated ANDRO-induced cytotoxicity and apoptosis.
Furthermore, BSO pretreatment augmented ANDRO-decreased expression of
antioxidant protein thioredoxin 1 (Trx1), while DTT reversed this
decrease. Further results showed that ANDRO increased the activity of
the GSH-related antioxidant enzyme glutathione peroxidase (GPx) and
the production of intracellular reactive oxygen species (ROS). Taken
together, this study demonstrates that the intracellular redox system
plays important roles in regulating the cytotoxicity of ANDRO on
hepatoma Hep3B cells.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 19695125 [PubMed - in process]
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