Nobiletin bioactivation in MDA-MB-468 breast cancer cells by cytochrome P450 CYP1 enzymes.

Date

2018-01-31

Advisors

Journal Title

Journal ISSN

ISSN

0278-6915

Volume Title

Publisher

Elsevier

Type

Article

Peer reviewed

Yes

Abstract

Nobiletin is a fully methoxylated flavone that has demonstrated anticancer activity via multiple modes of action. In the present study, the metabolism and further antiproliferative activity of nobiletin was evaluated in the CYP1 expressing human breast cancer cell line MDA–MB–468 and the normal breast cell line MCF10A. Nobiletin was metabolized in MDA–MB–468 cells to a single-demethylated derivative assigned NP1. This metabolite was absent in MCF10A cells that did not express CYP1 enzymes. Nobiletin exhibited submicromolar IC50 (0.1±0.04 μM) in MDA–MB–468 cells, whereas it was considerably less active in MCF10A cells (40 μM). In the presence of the CYP1 inhibitor acacetin, the conversion of nobiletin to NP1 was significantly reduced in MDA–MB–468 cells. Furthermore, a significant increase was noted in the population of the cells at the G1 phase, following treatment with nobiletin (10 μM) for 24 h compared with the control cells treated with DMSO (0.1%) alone (55.9±0.14 vs. 45.6±1.96), whereas the cell cycle of MCF10A cells was not significantly altered under the same treatment conditions. Taken collectively, the results suggest that nobiletin is selectively bioactivated in MDA–MB–468 breast cancer cells via metabolism by the CYP1 family of enzymes.

Description

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link

Keywords

Flavonoids, nobiletin, Cytochrome P450, Antiproliferation, cancer

Citation

Surichan, S., Arroo, R.R., Ruparelia, K., Tsatsakis, A.M., Androutsopoulos, V.P. (2018) Nobiletin bioactivation in MDA-MB-468 breast cancer cells by cytochrome P450 CYP1 enzymes. Food and Chemical Toxicology, 113, pp. 228-235.

Rights

Research Institute

Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)