Xanthones from the botanical dietary supplement mangosteen (Garcinia mangostana) with aromatase inhibitory activity

Abstract

Twelve xanthone constituents of the botanical dietary supplement mangosteen (the pericarp of Garcinia mangostana) were screened using a noncellular, enzyme-based microsomal aromatase inhibition assay. Of these compounds, garcinone D (3), garcinone E (5), alpha-mangostin (8), and gamma-mangostin (9) exhibited dose-dependent inhibitory activity. In a follow-up cell-based assay using SK-BR-3 breast cancer cells that express high levels of aromatase, the most potent of these four xanthones was gamma-mangostin (9). Because xanthones may be consumed in substantial amounts from commercially available mangosteen products, the consequences of frequent intake of mangosteen botanical dietary supplements require further investigation to determine their possible role in breast cancer chemoprevention.

Figure 1

Percent control activity (PCA) of extracts (at 20 µg/mL) and compounds (at 20 µg/mL) from mangosteen (G. mangostana) tested in a noncellular, enzyme-based, microsomal aromatase bioassay (DMSO = dimethylsulfoxide, blank/negative control; AG = aminoglutethimide, positive control, 50 µM).

Figure 2

IC₅₀ curves for active compounds from mangosteen: (A) garcinone D (3, IC₅₀ = 5.16 µM), (B) garcinone E (4, IC₅₀ = 25.14 µM), (C) α-mangostin (8, IC₅₀ = 20.66 µM), and (D) γ-mangostin (9, IC₅₀ = 6.88 µM).

Figure 3

Percent control activity (PCA) of extracts (at 20 µg/mL) and compounds (at 50 µM) from mangosteen (G. mangostana) tested in a SK-BR-3 cell-based aromatase bioassay (DMSO = dimethylsulfoxide, blank/negative control; Let = letrozole, positive control, 10 nM)).

Figure 4

Percent cell survival of extracts and compounds from mangosteen (G. mangostana) tested in a SK-BR-3 cell-based cytotoxicity bioassay (DMSO = dimethylsulfoxide, blank/negative control).

Figure 5

IC₅₀ curves for γ-mangostin (9) in (A) SK-BR-3 aromatase bioassay (IC₅₀ = 4.97 µM), and (B) SK-BR-3 cytotoxicity bioassay (IC₅₀ = 25.99 µM).