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- Title
Melissoidesin G, a diterpenoid purified from Isodon melissoides, induces leukemic-cell apoptosis through induction of redox imbalance and exhibits synergy with other anticancer agents.
- Authors
Yu, Zu-Yin; Liang, Yu-Guang; Xiao, He; Shan, Ya-Jun; Dong, Bo; Huang, Rui; Fu, Ya-Li; Zhao, Zhen-Hu; Liu, Ze-Yuan; Zhao, Qin-Shi; Wang, Sheng-Qi; Chen, Jia-Pei; Mao, Bing-Zhi; Cong, Yu-Wen
- Abstract
Melissoidesin G (MOG) is a new diterpenoid purified from Isodon melissoides, a plant used in Chinese traditional medicine as antitumor and anti-inflammatory agents. In our study, MOG was shown to specifically inhibit the growth of human leukemia cell lines and primary acute myeloid leukemia (AML) blasts via induction of apoptosis, with the evidence of mitochondrial ΔΨm loss, reactive oxygen species production, caspases activation and nuclear fragmentation. Furthermore, it was shown that thiol-containing antioxidants completely blocked MOG-induced mitochondrial ΔΨm loss and subsequent cell apoptosis, while the inhibition of apoptosis by benzyloxy-carbonyl-Val-Ala-Asp-fluoromethylketone only partially attenuated mitochondrial ΔΨm loss, indicating that MOG-induced redox imbalance is an early event upstream to mitochondrial ΔΨm loss and caspase-3 activation. Consistently, it was found that MOG rapidly decreased the intracellular glutathione (GSH) content in a dose-dependent manner and the significance of GSH depletion in MOG-induced apoptosis was further supported by the protective effects of tert-butylhydroquinone (tBHQ) and the facilitative effects of
- Publication
International Journal of Cancer, 2007, Vol 121, Issue 9, p2084
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.22945