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4-XL-PPD, a novel ginsenoside derivative, as potential therapeutic agents for gastric cancer shows anti-cancer activity via inducing cell apoptosis medicated generation of reactive oxygen species and inhibiting migratory and invasive.
- Source :
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Biomedicine & Pharmacotherapy . Oct2019, Vol. 118, pN.PAG-N.PAG. 1p. - Publication Year :
- 2019
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Abstract
- • A dammarane derivative (4-XL-PPD) was obtained by structural modification. • 4-XL-PPD showed much better anticancer activity than original compound AD-2 on cancer cells. • 4-XL-PPD-induction of apoptosis of can be attenuated by the ROS scavenger N-acetylcysteine in gastric carcinoma cells. • 4-XL-PPD inhibits migratory and invasive. (20 R)-Dammarane-3 β , 12 β , 20, 25-tetrol (25-OH-PPD) is a ginsenoside isolated from Panax ginseng (C. A. Meyer). Previous research shows that the compound exhibits anti-cancer activities on many human cancer cell lines. In an attempt to enhance 25-OH-PPD activity, some derivatives were synthesized. Through screening of the derivative compounds for anti-cancer activity against gastric carcinoma cells, 12 β - O -(L-Chloracetyl)-dammar-20(22)-ene-3 β , 25-diol (4-XL-PPD) was selected as a strong anti-cancer agent. In this study, the anti-cancer mechanisms of 4-XL-PPD were investigated. The results showed that compound 4-XL-PPD resulted in a concentration-dependent inhibition of cells viability in gastric cancer cells, without affecting the viability of normal cell (human gastric epithelial cell line-GES-1). In BGC-803 cancer cells, 4-XL-PPD triggered apoptosis, and stimulated reactive oxygen species production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. Meantime, 4-XL-PPD effectively suppressed the migratory and invasive capabilities of BGC-803 cancer cell and inhibited the expression levels of proteins associated with migratory and invasive capabilities (MMP-2, MMP-9, E-cadherin and CD34). All the results suggest that 4-XL-PPD exhibited remarkable anticancer activity base on inducing apoptosis via generating reactive oxygen species and inhibiting migratory and invasive, which support development of 4-XL-PPD as a potential agent for cancer therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 07533322
- Volume :
- 118
- Database :
- Academic Search Index
- Journal :
- Biomedicine & Pharmacotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 138668527
- Full Text :
- https://doi.org/10.1016/j.biopha.2019.01.050