title: Luteolin inhibits progestin-dependent angiogenesis, stem cell-like characteristics, and growth of human breast cancer xenografts.
abstract: OBJECTIVE
  Clinical trials and epidemiological evidence have shown that combined estrogen/progestin hormone replacement therapy, but not estrogen therapy alone, increases breast cancer risk in post-menopausal women. Previously we have shown that natural and synthetic progestins, including the widely used synthetic progestin medroxyprogesterone acetate (MPA), increase production of a potent angiogenic factor, vascular endothelial growth factor (VEGF), in human breast cancer cells, potentially providing an explanation for progestin's mechanism of action. Here, we tested the effects of luteolin (LU), a flavonoid commonly found in fruits and vegetables, on inhibiting progestin-dependent VEGF induction and angiogenesis in human breast cancer cells, inhibiting stem cell-like characteristics, as well as breast cancer cell xenograft tumor growth in vivo and expression of angiogenesis markers.
  
  
  METHODS
  Viability of both T47-D and BT-474 cells was measured using sulforhodamine B assays. Enzyme-linked immunosorbent assays were used to monitor VEGF secretion from breast cancer cells. Progestin-dependent xenograft tumor growth was used to determine LU effects in vivo. CD31 immunohistochemistry was used to determine blood-vessel density in xenograft tumors. CD44 expression, aldehyde dehydrogenase activity, and mammosphere-formation assays were used to monitor stem cell-like characteristics of breast cancer cells.
  
  
  RESULTS
  Luteolin treatment reduced breast cancer cell viability, progestin-dependent VEGF secretion from breast cancer cells, and growth of MPA-dependent human breast cancer cell xenograft tumors in nude mice. LU treatment also decreased xenograft tumor VEGF expression and blood-vessel density. Furthermore, LU blocked MPA-induced acquisition of stem cell-like properties by breast cancer cells.
  
  
  CONCLUSIONS
  Luteolin effectively blocks progestin-dependent human breast cancer tumor growth and the stem cell-like phenotype in human breast cancer cells.
authors: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211 USA ; Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Drive, Columbia, MO 65211 USA.
authors: Matthew T
authors: MT
authors: Cook
authors: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211 USA ; Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Drive, Columbia, MO 65211 USA.
authors: Yayun
authors: Y
authors: Liang
authors: IDEXX BioResearch, Columbia, MO 65202 USA.
authors: Cynthia
authors: C
authors: Besch-Williford
authors: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211 USA ; Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Drive, Columbia, MO 65211 USA.
authors: Sandy
authors: S
authors: Goyette
authors: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211 USA ; Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Drive, Columbia, MO 65211 USA.
authors: Benford
authors: B
authors: Mafuvadze
authors: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211 USA ; Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Drive, Columbia, MO 65211 USA.
authors: Salman M
authors: SM
authors: Hyder
keywords: Breast cancer; Luteolin; Medroxyprogesterone acetate; Therapeutic; Tumor growth