Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis.

Udhane, Sameer S; Dick, Bernhard; Hu, Qingzhong; Hartmann, Rolf W; Pandey, Amit V (2016). Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis. Biochemical and biophysical research communications, 477(4), pp. 1005-1010. Academic Press 10.1016/j.bbrc.2016.07.019

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The orteronel, abiraterone and galeterone, which were developed to treat castration resistant prostate cancer, inhibit 17,20 lyase activity but little is known about their effects on adrenal androgen biosynthesis. We studied the effect of several inhibitors and found that orteronel was selective towards 17,20 lyase activity than abiraterone and galeterone. Gene expression analysis showed that galeterone altered the expression of HSD3B2 but orteronel did not change the expression of HSD3B2, CYP17A1 and AKR1C3. The CYP19A1 activity was not inhibited except by compound IV which lowered activity by 23%. Surprisingly abiraterone caused complete blockade of CYP21A2 activity. Analysis of steroid metabolome by gas chromatography - mass spectrometry revealed changes in steroid levels caused by different inhibitors. We can conclude that orteronel is a highly specific inhibitor of 17,20 lyase activity. The discovery of these specific drug actions on steroidogenic enzyme activities would be valuable for understanding the regulation of androgens.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Other Institutions > Teaching Staff, Faculty of Medicine

UniBE Contributor:

Pandey, Amit Vikram

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0006-291X

Publisher:

Academic Press

Funders:

[4] Swiss National Science Foundation

Projects:

[102] Pathogenesis of disorders caused by human P450 oxidoreductase mutations Official URL

Language:

English

Submitter:

Amit Vikram Pandey

Date Deposited:

22 Sep 2016 09:46

Last Modified:

28 Jan 2018 21:55

Publisher DOI:

10.1016/j.bbrc.2016.07.019

PubMed ID:

27395338

Uncontrolled Keywords:

Abiraterone; CYP17A1; CYP21A2; Castration resistant prostate cancer; Orteronel; PCOS; Premature adrenarche

BORIS DOI:

10.7892/boris.88462

URI:

https://boris.unibe.ch/id/eprint/88462

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