期刊
PHYTOCHEMISTRY LETTERS
卷 52, 期 -, 页码 7-9出版社
ELSEVIER
DOI: 10.1016/j.phytol.2022.08.010
关键词
Uvaria rufa; Nephelium hypoleucum; TRAIL-resistance; Apoptosis
资金
- KAKENHI
- Japan Society for the Promotion of Science
- [20H03394]
- [20K16024]
Bioactivity-guided isolation of Uvaria rufa leaves and Nephelium hypoleucum bark led to the discovery of nine compounds with a new polyoxygenated cyclohexene scaffold. These compounds exhibited TRAIL resistance-overcoming activity and increased inhibition of gastric cancer cell line. Compounds 3 and 9 were found to sensitize AGS cells to apoptosis via both extrinsic and intrinsic pathways.
Bioactivity-guided isolation of Uvaria rufa leaves and Nephelium hypoleucum bark resulted in the successful isolation of nine compounds (1-9) bearing a new polyoxygenated cyclohexene scaffold: zeylenol-6-shikimate (1), (-)-zeylenol (2), microcarpin A (3), uvarigranol F (4), quercetin (5), kaempferol (6), and p-coumaric acid (7) from U. rufa, and epicatechin (8) and cinnamtannin B1 (9) from N. hypoleucum. The structures of the isolated compounds were elucidated using various spectroscopic techniques. All compounds, except for 7, exhibited weak-to-strong TRAIL-resistance-overcoming activity and an increased gastric cancer cell line (AGS) inhibition by 17-32% as compared to the treatment with the compounds alone. Compounds 3 and 9 were studied for their ability to overcome TRAIL resistance using western blot analysis, which indicated that they sensitised AGS cells to apoptosis via both extrinsic and intrinsic pathways by increasing the expression of several proapoptotic proteins (cleaved caspase-3,-8, and-9) and by decreasing the expression of anti-apoptotic protein Bcl-2.
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