Effects and mechanism of flavonoids from Astragalus complanatus on breast cancer growth

Naunyn Schmiedebergs Arch Pharmacol. 2015 Sep;388(9):965-72. doi: 10.1007/s00210-015-1127-0. Epub 2015 Apr 24.

Abstract

Flavonoids from Astragalus complanatus R.Br (FAC) had anticancer effects on many tumor cells. The current study was performed to evaluate the effects of FAC on human breast cell proliferation, apoptosis, and metastasis, as well as their active mechanism. Cell viability and growth were detected using the cell counting kit (CCK)-8 assay in vitro. Assay of FAC on induced breast cancer mortality was counted as survival time of nude mice after breast cell line inoculation. The effect of FAC on cell invasion was investigated by an optimization assay that contains a 96-well Boyden chamber with wells precoated with BME at three different concentrations. The mechanism of its action on apoptosis and metastasis was determined by related gene detection. Proliferation of three breast cell lines was inhibited with FAC treatment in a dose-dependent manner. Survival time of nude mice with breast cancer cell inoculation also was prolonged with increasing FAC dose. Metastasis in FAC-treated breast cells was also significantly inhibited. Real-time polymerase chain reaction (PCR) assay demonstrated that apoptosis-related BCL-2 and caspase-9 gene expression was consistent with their phenotype change. Metastasis-related FAK and BRCA1 gene expression was inversely related to FAC treatment. Western blot analysis indicated that BCL-2 and FAK proteins were reduced, whereas caspase-9 and BRCA1 proteins were increased with a higher dose of FAC treatment. These data suggested that FAC has an important role in breast cancer growth and metastasis suppression in vitro and in vivo. Its active mechanism involves promoting programmed cancer cell death and regulates metastasis-related gene expression.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Astragalus Plant / chemistry*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Flavonoids / administration & dosage
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / prevention & control
  • Real-Time Polymerase Chain Reaction
  • Survival Rate

Substances

  • Antineoplastic Agents, Phytogenic
  • Flavonoids