Home >> Redox Report, Volume 14, Number 4

Intracellular glutathione regulates Andrographolide-induced cytotoxicity on hepatoma Hep3B cells

Authors: Ji, Lili1; Shen, Kaikai2; Liu, Jun3; Chen, Ying2; Liu, Tianyu2; Wang, Zhengtao4

Source: Redox Report, Volume 14, Number 4, August 2009 , pp. 176-184(9)

Publisher: Maney Publishing

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Abstract:

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.

Keywords: APOPTOSIS; GLUTATHIONE; ANDROGRAPHOLIDE; HEPATOMA HEP3B CELL

Document Type: Research Article

DOI: http://dx.doi.org/10.1179/135100009X466122

Affiliations: 1: 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; Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai, People's Republic China 2: 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 3: Department of Pharmaceutical Sciences, The University of Michigan, Ann Arbor, Michigan, USA 4: 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, Shanghai R&D Centre for Standardization of Chinese Medicines, 1200 Cailun Road, Shanghai 201203, People's Republic China; or jll_syc@yahoo.com.cn, Email: wangzht@hotmail.com

Publication date: 2009-08-01

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