In:
International Journal of Cancer, Wiley, Vol. 121, No. 9 ( 2007-11), p. 2084-2094
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 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 (As 2 O 3 ), doxorubicin or cisplatin. Additionally, the synergistic apoptotic effects of MOG with As 2 O 3 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. © 2007 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0020-7136
,
1097-0215
Language:
English
Publisher:
Wiley
Publication Date:
2007
detail.hit.zdb_id:
218257-9
detail.hit.zdb_id:
1474822-8
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