Angelica sinensis polysaccharides promotes apoptosis in human breast cancer cells via CREB-regulated caspase-3 activation

Biochem Biophys Res Commun. 2015 Nov 20;467(3):562-9. doi: 10.1016/j.bbrc.2015.09.145. Epub 2015 Sep 30.

Abstract

Angelica sinensis polysaccharide (ASP) is purified from the fresh roots of Angelica sinensis (AS). This traditional Chinese medicine has been used for thousands of years for treating gynecological diseases and used in functional foods for the prevention and treatment of various diseases, such as inflammation and cancer. The antitumor activity of ASP is related to its biological activities, because it suppresses a variety of pro-proliferative or anti-apoptotic factors that are dramatically expressed in cancer cells of given types. In this study, we show that angelica sinensis polysaccharide induced apoptosis in breast cancer cells of T47D over-expressing the Cyclic AMP response element binding protein (CREB), inducing apoptosis-related signaling pathway activity. The result also found that ASP caused cell death was linked to caspase activity, accompanied by the loss of mitochondrial membrane potential, cytochrome c release, and Bax translocation from the cytosol to the mitochondria. We found that ASP significantly affected the poly-ADP-ribose polymerase (PARP), Bcl-2 Associated X Protein (Bax), Bcl-2, Bcl-xL and apoptotic protease activating facter-1 (Apaf1) protein expression in a dose- and time-dependent manner. DAPI staining and Flow cytometry were used to analyze apoptosis. The nude mice xenograft model was used to evaluate the antitumor effect of ASP in vivo. ASP has profound antitumor effect on T47D cells, probably by inducing apoptosis through CREB signaling pathway. Thus, these results suggest that ASP would be a promising therapeutic agent for breast cancer.

Keywords: Angelica sinensis polysaccharide; Breast cancer; CREB; Caspases-3; T47D.

MeSH terms

  • Angelica sinensis / chemistry*
  • Animals
  • Apoptosis / drug effects*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Caspase 3 / metabolism*
  • Cell Line, Tumor
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Enzyme Activation
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Mitochondria / drug effects
  • Polysaccharides / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Polysaccharides
  • Caspase 3