Tracer experiment revealed that (<i>E</i>)-3″-hydroxygeranylhydroquinone is not an intermediate of the shikonin/alkannin and shikonofuran biosynthetic pathways in <i>Lithospermum erythrorhizon</i> DOI Open Access

Misaki Manabe,

Bunta Watanabe, Haruka Oshikiri

et al.

Plant Biotechnology, Journal Year: 2024, Volume and Issue: 41(3), P. 315 - 317

Published: July 28, 2024

Lithospermum erythrorhizon (Boraginaceae) produces shikonin/alkannin, an enantiomeric pair of red naphthoquinone pigments with diverse biological activities. For the industrial production shikonin/alkannin derivatives, a cell suspension culture system L. has been established. To produce derivatives more efficiently in cultured cells, it is essential to understand biosynthetic pathway, which not fully elucidated. A previous study suggested that conversion (Z)- (E)-3″-hydroxygeranylhydroquinone (3″-OH-GHQ) branching point pathway and shikonofuran cultures. However, clear whether (E)-3″-OH-GHQ intermediate both pathways. This performed feeding assay three deuterium-labeled compounds including its (Z)-isomer, showed was involved

Language: Английский

β,β-Dimethylacryloyl Alkannin from Arnebia euchroma Roots Suppresses Triple-Negative Breast Cancer Growth via AKT/Gli1 Signaling DOI
Yimeng Zhou, Jin Tae Kim,

Jung Won Kwon

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

After confirmation of Arnebia euchroma by genetic analysis, we identified the key compounds from root: alkannin (1), acetylalkannin (2), β-acetoxyisovaleryl (3), isobutyryl (4), and β,β-dimethylacryloyl (DMA) (5). Among these, DMA most effectively inhibited proliferation triple-negative breast cancer (TNBC) cells, with IC50 values 5.1 μM (MDA-MB-231) 8.7 (MCF10DCIS.com). Hedgehog (Hh) inhibitor Gant61 targeting Gli1 significantly induced apoptosis, as indicated increased Bax cleaved PARP, decreased Bcl-2 levels (p < 0.01) in both cell lines. We also AKT a potential target DMA, treatment reduced phosphorylated (Ser473) protein 66.3% ± 0.7% 30.1% 5.7% MDA-MB-231 MCF10DCIS.com respectively 0.01). In vivo, (25 mg/kg) suppressed xenograft tumor growth approximately 78% apoptosis through regulating AKT/Hh/Gli1 axis. Interestingly, form (5') lost its efficacy inhibiting proliferation, p-AKT expression, transcriptional activity nuclear localization, indicating that Michael acceptor is critical for TNBC growth. Overall, vitro vivo AKT/Gli1 pathway shows potent agent against TNBC.

Language: Английский

Citations

0
Tracer experiment revealed that (<i>E</i>)-3″-hydroxygeranylhydroquinone is not an intermediate of the shikonin/alkannin and shikonofuran biosynthetic pathways in <i>Lithospermum erythrorhizon</i> DOI Open Access

Misaki Manabe,

Bunta Watanabe, Haruka Oshikiri

et al.

Plant Biotechnology, Journal Year: 2024, Volume and Issue: 41(3), P. 315 - 317

Published: July 28, 2024

Lithospermum erythrorhizon (Boraginaceae) produces shikonin/alkannin, an enantiomeric pair of red naphthoquinone pigments with diverse biological activities. For the industrial production shikonin/alkannin derivatives, a cell suspension culture system L. has been established. To produce derivatives more efficiently in cultured cells, it is essential to understand biosynthetic pathway, which not fully elucidated. A previous study suggested that conversion (Z)- (E)-3″-hydroxygeranylhydroquinone (3″-OH-GHQ) branching point pathway and shikonofuran cultures. However, clear whether (E)-3″-OH-GHQ intermediate both pathways. This performed feeding assay three deuterium-labeled compounds including its (Z)-isomer, showed was involved

Language: Английский

Citations

1