Resorufin: a lead for a new protein kinase CK2 inhibitor.

Full Abstract

Screening a natural compound library led to the identification of resorufin as a highly selective and potent inhibitor of protein kinase CK2. Out of 52 kinases tested, only CK2 was inhibited, in contrast to emodin, a structurally related, known CK2 inhibitor that, in addition to CK2, inhibited ten other kinases by 90%. The IC50 values determined for the CK2 holoenzymes were 1.5 mol/l and for the free catalytic subunits ca. 4 mol/l. Altogether four cell lines were subjected to resorufin and emodin treatment. In the case of the three prostate carcinoma cell lines (PC-3, DU-145, LNCaP), 24 h treatment with 40 mol/l resorufin led to 15-20% dead cells; however, no caspase-mediated apoptosis was observed. In the case of the colorectal carcinoma HCT116 cell line, a similar picture was obtained, yet, when resorufin was administered to cells treated with doxorubicin, apoptosis was strongly induced within 24 h. Endogenous protein kinase CK2 was inhibited by resorufin by ca. 80% in the three prostate cell lines. In the case of the HCT116 cells, the inhibition was only 40% supporting the notion of cell line-specific selectivity. Moreover, we analysed the effect of resorufin and emodin on selected signalling molecules in the cell lines under investigation.

Author information

Author/s: Sandholt, Iben Skjøth (IS); Olsen, Birgitte Brinkmann (BB); Guerra, Barbara (B); Issinger, Olaf-Georg (OG);

Affiliation: Institute of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej Denmark.

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Anti-cancer drugs (Anticancer Drugs), published in England. (Language: eng)

Reference: 2009-Apr; vol 20 (issue 4) : pp 238-48

Dates: Created 2009/03/12; Completed 2009/05/15;

PMID: 19177021, status: MEDLINE (last retrieval date: 5/15/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Apoptosis - drug effects
Casein Kinase II - antagonists & inhibitors; metabolism
Cell Line, Tumor
Colorectal Neoplasms - drug therapy; pathology
Emodin - pharmacology
Humans

Inhibitory Concentration 50
Male
Oxazines - administration & dosage; pharmacology
Prostatic Neoplasms - drug therapy; pathology
Protein Kinase Inhibitors - administration & dosage; pharmacology
Signal Transduction - drug effects

Associated Chemicals: Oxazines (0) ; Protein Kinase Inhibitors (0) ; Emodin (518-82-1) ; resorufin (635-78-9) ; Casein Kinase II (EC 2.7.1.37)

This article has not been indexed for related articles as yet, however you can still use the live related article search links below.

See 100+ related articles.

See a large map of 100+ related articles.