3 research outputs found
Diastereotopic and Deuterium Effects in Gemini
Changing the geminal methyl groups
on 1α,25-dihydroxyvitamin
D<sub>3</sub> and its analogues to the deuterio versions generally
improves the bioactivity. Derivatives of 1α,25-dihydroxyvitamin
D<sub>3</sub> with two chains emanating at C20, commonly referred
to as gemini, are subject to the same phenomenon. Additionally, gemini
with different side chains are susceptible to bioactivity differentials
where the C17–C20 threo configuration usually imparts higher
activity than the corresponding erythro arrangement. In an effort
to analyze the deuterium effect on gemini with minimal diastereotopic
distortion, we synthesized gemini with equal side chains but introduced
deuterium diastereospecifically on either chain. We solved the crystal
structures of these compounds in the zebra fish zVDR ligand binding
domain as complexes with NCoA-2 coactivator peptide and correlated
the findings with growth inhibition in a breast cancer cell line
Sulforaphene Interferes with Human Breast Cancer Cell Migration and Invasion through Inhibition of Hedgehog Signaling
Although
inhibition of mammary tumorigenesis by isothiocyanates
has been widely studied, little is known about the effects of sulforaphene
on invasiveness of breast cancer. Here, sulforaphene significantly
inhibited the migration and invasion of triple-negative SUM159 human
breast cancer cells and suppressed the expression and activity of
matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). The Hedgehog
(Hh) pathway, as an upstream signaling modulator, was significantly
suppressed by sulforaphene. In particular, ciliary localization of
Gli1 and its nuclear translocation were blocked by sulforaphene in
a time-dependent manner. Consistently, downregulation of Hh signaling
by vismodegib and Gli1 knockdown reduced the cellular migration and
invasion as well as the expression of MMP-2 and MMP-9. These results
indicate that the suppression of Hh/Gli1 signaling by sulforaphene
may reduce the MMP-2 and MMP-9 activities and cellular invasiveness
of human breast cancer cells, suggesting the potential efficacy of
sulforaphene against breast cancer invasion and metastasis
Ellagic Acid Identified through Metabolomic Analysis Is an Active Metabolite in Strawberry (‘Seolhyang’) Regulating Lipopolysaccharide-Induced Inflammation
This study employed the metabolomic
approach to identify the key
constituent exerting anti-inflammatory activity in murine macrophage
RAW 264.7 cells. Among the six different fractions (SF1–SF6)
of the strawberry ‘Seolhyang’, SF4 showed more significant
inhibition on iNOS expression than SF3, and ellagic acid was determined
as the most significant different component between SF4 and SF3 using
orthogonal partial least-squares discriminant analysis. Ellagic acid
(0.3 and 1.0 μM) and SF4 (100 μg/mL) were found to regulate
the same inflammatory mediators, inhibitory κB (IκB) and
mitogen-activated protein kinases (MAPKs), which led to the reduction
of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β),
and iNOS expressions. These results demonstrate that ellagic acid
from strawberry ‘Seolhyang’ is the major component playing
a crucial role in inflammation, suggesting the possible application
of metabolomic analysis to determining the key ingredients having
biological functions in the complicated food matrix