A novel HIF-1 inhibitor--manassantin A derivative LXY6099 inhibits tumor growth.
- Author:
Fang-Fang LAI
;
Xiao-Yu LIU
;
Fei NIU
;
Li-Wei LANG
;
Ping XIE
;
Xiao-Guang CHEN
- Publication Type:Journal Article
- MeSH:
Animals;
Antineoplastic Agents;
pharmacology;
Breast Neoplasms;
metabolism;
Cell Line, Tumor;
Gene Expression Regulation, Neoplastic;
Heterografts;
Humans;
Hypoxia-Inducible Factor 1;
metabolism;
Lignans;
pharmacology;
Mice, Nude
- From:
Acta Pharmaceutica Sinica
2014;49(5):622-626
- CountryChina
- Language:Chinese
-
Abstract:
Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
