Chapter title |
Thiostrepton, a natural compound that triggers heat shock response and apoptosis in human cancer cells: a proteomics investigation.
|
---|---|
Chapter number | 21 |
Book title |
Advancements of Mass Spectrometry in Biomedical Research
|
Published in |
Advances in experimental medicine and biology, June 2014
|
DOI | 10.1007/978-3-319-06068-2_21 |
Pubmed ID | |
Book ISBNs |
978-3-31-906067-5, 978-3-31-906068-2
|
Authors |
Sandu C, Wetie AG, Darie CC, Steller H, Cristinel Sandu, Armand G. Ngounou Wetie, Costel C. Darie, Hermann Steller, Sandu, Cristinel, Wetie, Armand G. Ngounou, Darie, Costel C., Steller, Hermann |
Abstract |
Thiostrepton is a natural antibiotic produced by bacteria of Streptomyces genus. We identified Thiostrepton as a strong hit in a cell-based small molecule screen for DIAP1 stability modulators. It was shown previously that Thiostrepton induces upregulation of several gene products in Streptomyces lividans, including the TipAS and TipAL isoforms, and that it can induce apoptotic cell death in human cancer cells. Furthermore, it was suggested that thiostrepton induces oxidative and proteotoxic stress, as inferred from the transcriptional upregulation of stress-related genes and endoplasmic reticulum (ER) stress genes. We used a combination of biochemical and proteomics approaches to investigate the effect of Thiostrepton and other compounds in human cells. Our mass-spectrometry data and subsequent biochemical validation shows that Thiostrepton (and MG-132 proteasome inhibitor) trigger upregulation of heat shock proteins HspA1A, Hsp70, Hsp90α, or Hsp105 in various human cancer cells. We propose a model where Thiostrepton-induced proteasome inhibition leads to accumulation of protein aggregates that trigger a heat shock response and apoptosis in human cancer cells. |
X Demographics
Geographical breakdown
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 17 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 3 | 18% |
Student > Master | 3 | 18% |
Professor > Associate Professor | 2 | 12% |
Researcher | 2 | 12% |
Student > Ph. D. Student | 1 | 6% |
Other | 2 | 12% |
Unknown | 4 | 24% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 4 | 24% |
Biochemistry, Genetics and Molecular Biology | 2 | 12% |
Immunology and Microbiology | 2 | 12% |
Agricultural and Biological Sciences | 2 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 6% |
Other | 2 | 12% |
Unknown | 4 | 24% |