Bioactivity of Curcumin on the Cytochrome P450 Enzymes of the Steroidogenic Pathway.

Rodríguez Castaño, Patricia; Parween, Shaheena; Pandey, Amit Vikram (2019). Bioactivity of Curcumin on the Cytochrome P450 Enzymes of the Steroidogenic Pathway. International journal of molecular sciences, 20(18) Molecular Diversity Preservation International MDPI 10.3390/ijms20184606

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Turmeric, a popular ingredient in the cuisine of many Asian countries, comes from the roots of the Curcuma longa and is known for its use in Chinese and Ayurvedic medicine. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have potent wound healing, anti-inflammatory, and anti-carcinogenic activities. While curcuminoids have been studied for many years, not much is known about their effects on steroid metabolism. Since many anti-cancer drugs target enzymes from the steroidogenic pathway, we tested the effect of curcuminoids on cytochrome P450 CYP17A1, CYP21A2, and CYP19A1 enzyme activities. When using 10 µg/ml of curcuminoids, both the 17α-hydroxylase as well as 17,20 lyase activities of CYP17A1 were reduced significantly. On the other hand, only a mild reduction in CYP21A2 activity was observed. Furthermore, CYP19A1 activity was also reduced up to ~20% of control when using 1-100 µg/ml of curcuminoids in a dose-dependent manner. Molecular docking studies confirmed that curcumin could dock onto the active sites of CYP17A1, CYP19A1, as well as CYP21A2. In CYP17A1 and CYP19A1, curcumin docked within 2.5 Å of central heme while in CYP21A2 the distance from heme was 3.4 Å, which is still in the same range or lower than distances of bound steroid substrates. These studies suggest that curcuminoids may cause inhibition of steroid metabolism, especially at higher dosages. Also, the recent popularity of turmeric powder as a dilatory supplement needs further evaluation for the effect of curcuminoids on steroid metabolism. The molecular structure of curcuminoids could be modified to generate better lead compounds with inhibitory effects on CYP17A1 and CYP19A1 for potential drugs against prostate cancer and breast cancer.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders

UniBE Contributor:

Rodríguez Castaño, Patricia; Parween, Shaheena and Pandey, Amit Vikram

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1661-6596

Publisher:

Molecular Diversity Preservation International MDPI

Language:

English

Submitter:

Karen Lidzba

Date Deposited:

28 Jan 2020 12:46

Last Modified:

29 Jan 2020 11:35

Publisher DOI:

10.3390/ijms20184606

PubMed ID:

31533365

Uncontrolled Keywords:

CYP19A1 E100 aromatase curcumin curcuminoid cytochrome P450 diferuloylmethane estrogen synthase

BORIS DOI:

10.7892/boris.138674

URI:

https://boris.unibe.ch/id/eprint/138674

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