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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-9-16
pubmed:abstractText
Tanshinone I (Tan I), a diterpene quinone extracted from herbal medicine Salvia miltiorrhiza Bunge, has recently been reported to have antitumor effects. As the mechanism of its proapoptotic effects on human myeloid leukemia cells has not been extensively studied, we performed an in-depth evaluation of the effects of Tan I on apoptosis in human K562 and HL-60 cells. The results revealed that Tan I could inhibit the growth of leukemia cells and cause apoptosis in a time- and dose-dependent manner. Apoptosis was observed clearly by flow cytometry and Hoechst 33258 staining, as well as DNA fragmentation analysis. After treatment by Tan I for 48 h, the percentage of disruption of mitochondrial membrane potential (??m) was increased in a dose-dependent manner. Western blotting analysis demonstrated the cleavage of caspase-3 zymogen protein and a dose-dependent cleavage of poly-(ADP-ribose) polymerase. Tan I-induced apoptosis was accompanied by a significant decrease in survivin and an increase in Bax. Moreover, Tan I treatment remarkably downregulated the phosphorylation of both P85/PI3K and Akt in a time-dependent manner, and the PI3K/AKT-specific inhibitor (LY294002) mimicked the apoptosis-inducing effects of Tan I. We therefore conclude that the induction of apoptosis by Tan I in these leukemia cells is mainly related to the disruption of ??m, the upregulation of Bax expression, and the activation of caspase-3. This process is highly correlated with the inactivation of PI3K/Akt/survivin signaling pathways. The results indicate that Tan I may serve as an effective adjunctive reagent in the treatment of leukemia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1432-0584
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1089-97
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20512574-Antineoplastic Agents, Phytogenic, pubmed-meshheading:20512574-Apoptosis, pubmed-meshheading:20512574-Caspase 3, pubmed-meshheading:20512574-DNA Fragmentation, pubmed-meshheading:20512574-Diterpenes, Abietane, pubmed-meshheading:20512574-Drugs, Chinese Herbal, pubmed-meshheading:20512574-Enzyme Activation, pubmed-meshheading:20512574-HL-60 Cells, pubmed-meshheading:20512574-Humans, pubmed-meshheading:20512574-K562 Cells, pubmed-meshheading:20512574-Leukemia, Myeloid, pubmed-meshheading:20512574-Membrane Potential, Mitochondrial, pubmed-meshheading:20512574-Molecular Structure, pubmed-meshheading:20512574-Phenanthrenes, pubmed-meshheading:20512574-Phosphatidylinositol 3-Kinases, pubmed-meshheading:20512574-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20512574-Signal Transduction
pubmed:year
2010
pubmed:articleTitle
Inactivation of PI3k/Akt signaling pathway and activation of caspase-3 are involved in tanshinone I-induced apoptosis in myeloid leukemia cells in vitro.
pubmed:affiliation
Hematological Department and Institute, Third Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China. jiajunliu2002@yahoo.com.cn
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't