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Gambogic acid is cy...
Gambogic acid is cytotoxic to cancer cells through inhibition of the ubiquitin-proteasome system
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- Felth, Jenny, 1979- (author)
- Uppsala universitet,Avdelningen för farmakognosi
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- Lesiak-Mieczkowska, Karolina (author)
- Cancer Center Karolinska, Department of Oncology-Pathology, Karolinska Institute
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- Haglund, Caroline (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Gullbo, Joachim (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Larsson, Rolf (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Linder, Stig (author)
- Karolinska Institutet
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- Bohlin, Lars (author)
- Uppsala universitet,Avdelningen för farmakognosi
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- Fryknäs, Mårten (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Rickardson, Linda (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- D'Arcy, P (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2012-11-20
- 2013
- English.
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In: Investigational new drugs. - : Springer Science and Business Media LLC. - 0167-6997 .- 1573-0646. ; 31:3, s. 587-598
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Gambogic acid (GA), displays cytotoxicity towards a wide variety of tumor cells and has been shown to affect many important cell-signaling pathways. In the present work, we investigated the mechanism of action of GA by analysis of drug-induced changes in gene expression profiles and identified GA and the derivative dihydro GA as possible inhibitors of the ubiquitin-proteasome system (UPS). Both GA and dihydro GA inhibited proteasome function in cells resulting in the accumulation of polyubiquitin complexes. In vitro experiments showed that both GA and dihydro GA inhibited 20S chymotrypsin activity and the inhibitory effects of GA and dihydro GA on proteasome function corresponded with apoptosis induction and cell death. In conclusion, our results show that GA and dihydro GA exert their cytotoxic activity through inhibition of the UPS, specifically by acting as inhibitors of the chymotrypsin activity of the 20S proteasome.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- gambogic acid
- cancer
- cytotoxic
- proteasome inhibition
- Pharmacognosy
- Farmakognosi
- Clinical pharmacology
- Klinisk farmakologi
- Pharmacognosy
- Farmakognosi
- Clinical Pharmacology
- Klinisk farmakologi
Publication and Content Type
- vet (subject category)
- art (subject category)
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Felth, Jenny, 19 ...
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Lesiak-Mieczkows ...
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Haglund, Carolin ...
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Gullbo, Joachim
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Larsson, Rolf
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Linder, Stig
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show more...
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Bohlin, Lars
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Fryknäs, Mårten
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Rickardson, Lind ...
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D'Arcy, P
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show less...
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- MEDICAL AND HEALTH SCIENCES
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and Basic Medicine
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmacology and ...
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Uppsala University
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Karolinska Institutet