title: Andrographolide inhibits hypoxia-inducible factor-1 through phosphatidylinositol 3-kinase/AKT pathway and suppresses breast cancer growth.
abstract: Hypoxia-inducible factor-1 (HIF-1) is a master regulator of the transcriptional response to hypoxia. HIF-1α is one of the most compelling anticancer targets. Andrographolide (Andro) was newly identified to inhibit HIF-1 in T47D cells (a half maximal effective concentration [EC50] of 1.03×10(-7) mol/L), by a dual-luciferase reporter assay. It suppressed HIF-1α protein and gene accumulation, which was dependent on the inhibition of upstream phosphatidylinositol 3-kinase (PI3K)/AKT pathway. It also abrogated the expression of HIF-1 target vascular endothelial growth factor (VEGF) gene and protein. Further, Andro inhibited T47D and MDA-MB-231 cell proliferation and colony formation. In addition, it exhibited significant in vivo efficacy and antitumor potential against the MDA-MB-231 xenograft in nude mice. In conclusion, these results highlighted the potential effects of Andro, which inhibits HIF-1, and hence may be developed as an antitumor agent for breast cancer therapy in future.
authors.affiliation: Department of General Surgery, Beijing Chao-Yang Hospital, Beijing, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of General Surgery, Beijing Chao-Yang Hospital, Beijing, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Beijing Chao-Yang Hospital, Beijing, People's Republic of China.
authors.forename: Hongchuan
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Gynaecology and Obstetrics, Beijing Chao-Yang Hospital, Beijing, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Cheng
keywords: Andrographolide (Andro); HIF-1α; PI3k/AKT/mTOR pathway; breast cancer; hypoxia; inhibit