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

Rodríguez Castaño Rodríguez Castaño,Parween Parween,Pandey Pandey

doi:10.3390/ijms20184606

Rodríguez Castaño Rodríguez Castaño, Parween Parween + Show 1 more

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https://doi.org/10.3390/ijms20184606

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Abstract

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.

Highlights

Turmeric, the well-known yellow spice and coloring agent, is found in the cuisine of numerous Asian countries
A stock solution of curcuminoids was made in ethanol
Computational docking from our experiments showed that curcumin could bind into the active sites of steroid metabolizing P450s

Summary

Introduction

The well-known yellow spice and coloring agent, is found in the cuisine of numerous Asian countries. Curcumin (CI-75300, diferuloylmethane, E100, Natural Yellow 3) is the most abundant of the curcuminoids and enhances wound healing, modulates angiogenesis and the immune system, and has anti-inflammatory, anti-oxidant, anti-infective and anti-cancer activities [3]. Since the discovery of curcumin as a bioactive compound, many biological activities have been described [4]. Curcumin has been shown to modulate molecular signaling pathways, such as the aryl hydrocarbon receptor, the induction of Nuclear factor erythroid 2-related factor 2 (Nrf2) or the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), initiating the activation of inflammatory and immunogenic factors. Curcumin can inhibit angiogenesis and induce apoptosis on cancerous cells [5,6]. Curcumin is involved in the increase of insulin in plasma and the decrease of blood glucose in diabetic patients [7,8]

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