Background: Turmeric is a popular ingredient in the cuisine of many Asian countries. It is also known for its use in Chinese and Ayurvedic medicine. It comes from the root of the Curcuma longa. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcumin has potent anti-inflammatory and anti-carcinogenic activities. Since many anti-cancer drugs target enzymes from the steroidogenic pathway, we tested the bioactivity of curcuminoids on CYP17A1, CYP21A2, and CYP19A1 activities.
Methods: Curcuminoids were extracted from turmeric with organic solvents. We conducted a cell-based assay for CYP17A1 and CYP21A2 activities using human adrenal cell line NCI-H295R. 3H-pregnenolone was used for CYP17A1 assays, and 3H-17a-hydroxyprogesterone was used as a substrate for CYP21A2. Curcuminoids were added at different concentrations and incubated for 24h. Steroids were separated by thin layer chromatography and analyzed by phosphorimager analysis. For CYP19A1 activity, an in vitro assay using endoplasmic reticulum from JEG3 were used with 3H-androstenedione as the substrate. Curcuminoids were incubated for 1h, and the formation of 3H-water from the androstenedione breakdown was measured by scintillation counting.
Results: The CYP17A1 hydroxylase activity, when using 10 µg/ml of curcuminoids, was reduced to ~15%, whereas CYP17A1 lyase activity was reduced to ~30% of control. On the other hand, CYP21A2 activity was only reduced to a ~50%. Furthermore, CYP19A1 activity was reduced to 80~20% when using 1-100 µg/ml of curcuminoids in a dose-dependent manner. No effect on the activity of 5a-reductase for conversion of testosterone to dihydrotestosterone was observed.
Conclusions: These studies show that curcuminoids may potentially cause some inhibition of steroid metabolism, especially at higher dosages. The activities of CYP17A1 and CYP19A1 were inhibited by curcuminoids which indicates potential the anti-carcinogenic effects in case of prostate cancer as well as breast cancer which can be targeted by inhibition of steroidogenesis. Also, the recent popularity of turmeric powder/curcumin as a dilatory supplement needs further evaluation of the effect of curcuminoids on steroid metabolism.
19 Sep 2019 - 21 Sep 2019