Melissoidesin G, a diterpenoid purified from Isodon melissoides, induces leukemic-cell apoptosis through induction of redox imbalance and exhibits synergy with other anticancer agents
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
2007-11-01
发表期刊INTERNATIONAL JOURNAL OF CANCER
ISSN0020-7136
卷号121期号:9页码:2084-2094
摘要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 Delta Psi m loss, reactive oxygen species production, caspases activation and nuclear fragmentation. Furthermore, it was shown that thiol-containing antioxidants completely blocked MOG-induced mitochondrial Delta Psi m loss and subsequent cell apoptosis, while the inhibition of apoptosis by benzyloxy-carbonyl-Val-Ala-Asp-fluoromethylketone only partially attenuated mitochondrial Delta Psi m loss, indicating that MOG-induced redox imbalance is an early event upstream to mitochondrial Delta Psi m 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-butyl hvdroquinone (tBHQ) and the facilitative effects of DL-buthionine (S,R)-sulfoximine (BSO). Furthermore, it was showed that GSH depletion induced by MOG rendered some leukemia cell lines more sensitive to arsenic trioxide (As2O3), doxorubicin or cisplatin. Additionally, the synergistic apoptotic effects of 1106 with As2O3 were detected in HL-60 and primary AML cells, but not in normal cells, suggesting the selective toxicity of their combination to the malignant cells. Together, we proposed that MOG alone or administered with other anticancer agents may provide a novel therapeutic strategy for leukemia. (C) 2007 Wiles-Liss. Inc.
关键词Melissoidesin g Leukemia Apoptosis Redox Arsenic Trioxide
收录类别sci
语种英语
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/1683
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Beijing Inst Radiat Med, Dept Pathophysiol, Beijing 100850, Peoples R China
2.Beijing 307 Hosp, Acad Med Sci, Dept Clin Pharmacol, Beijing, Peoples R China
3.Chinese Acad Med Sci, Inst Basic Med Sci, Dept Mol Immunol, Beijing 100730, Peoples R China
4.Chinese Acad Med Sci, Kunming Inst Bot, Dept Phytochem, Kunming, Yunnan, Peoples R China
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Yu, Zu-Yin,Liang, Yu-Guang,Xiao, He,et al. Melissoidesin G, a diterpenoid purified from Isodon melissoides, induces leukemic-cell apoptosis through induction of redox imbalance and exhibits synergy with other anticancer agents[J]. INTERNATIONAL JOURNAL OF CANCER,2007,121(9):2084-2094.
APA Yu, Zu-Yin.,Liang, Yu-Guang.,Xiao, He.,Shan, Ya-Jun.,Dong, Bo.,...&Cong, Yu-Wen.(2007).Melissoidesin G, a diterpenoid purified from Isodon melissoides, induces leukemic-cell apoptosis through induction of redox imbalance and exhibits synergy with other anticancer agents.INTERNATIONAL JOURNAL OF CANCER,121(9),2084-2094.
MLA Yu, Zu-Yin,et al."Melissoidesin G, a diterpenoid purified from Isodon melissoides, induces leukemic-cell apoptosis through induction of redox imbalance and exhibits synergy with other anticancer agents".INTERNATIONAL JOURNAL OF CANCER 121.9(2007):2084-2094.
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