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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Piao, Jin-Lan Cui, Zheng-Guo Furusawa, Yukihiro Ahmed, Kanwal Rehman, Mati Ur Tabuchi, Yoshiaki Kadowaki, Makoto Kondo, Takashi |
| Description | Country affiliation: Japan Author Affiliation: Piao JL ( Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.) |
| Abstract | Shikonin (SHK), a natural naphthoquinone derived from the Chinese medical herb Lithospermum erythrorhizon, induces both apoptosis and necroptosis in several cancer cell lines. However, the detailed molecular mechanisms involved in the initiation of cell death are still unclear. In the present study, caspase-dependent apoptosis was induced by SHK treatment at 1µM after 6h in U937 cells, with increase in DNA fragmentation, generation of intracellular reactive oxygen species (ROS), fraction of cells with low mitochondrial membrane potential (MMP), and in the expression of BH3 only proteins Noxa and tBid. Interestingly, caspase-independent cell death was also detected with SHK treatment at 10µM, observed as increase in SYTOX® Green staining and release of lactate dehydrogenase (LDH). Necrostatin-1 (Nec-1) completely inhibited the SHK-induced leakage of LDH and SYTOX® Green staining. Cell permeable exogenous glutathione (GSH) completely inhibited 1µM SHK-induced apoptosis and converted 10µM SHK-induced necroptosis to apoptosis. Gene expression profiling revealed that 353 genes were found to be significantly regulated by 1µM and 85 genes by 10µM of SHK treatment, respectively. Among these genes, the transcription factor 3 (ATF3) and DNA-damage-inducible transcript 3 (DDIT3) were highly expressed at 1µM of SHK treatment, while tumor necrosis factor (TNF) expression mainly increased at 10µM treatment. These findings provide novel information for the molecular mechanism of SHK-induced apoptosis and necroptosis. |
| File Format | HTM / HTML |
| ISSN | 00092797 |
| Issue Number | 2 |
| Volume Number | 205 |
| e-ISSN | 18727786 |
| Journal | Chemico-Biological Interactions |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-09-25 |
| Publisher Place | Ireland |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Biochemistry Discipline Pharmacology Antineoplastic Agents, Phytogenic Pharmacology Apoptosis Drug Effects Cell Death Naphthoquinones Administration & Dosage Genetics Physiology Apoptosis Regulatory Proteins Caspases Metabolism Drugs, Chinese Herbal Gene Expression Gene Expression Profiling Glutathione Humans Necrosis Oxidative Stress U937 Cells Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Toxicology |
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