Anthocyanin induces apoptosis of DU-145 cells in vitro and inhibits xenograft growth of prostate cancer

Yonsei Med J. 2015 Jan;56(1):16-23. doi: 10.3349/ymj.2015.56.1.16.

Abstract

Purpose: To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model).

Materials and methods: The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2×10⁶) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated.

Results: Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth.

Conclusion: This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model.

Keywords: Prostatic neoplasms; anthocyanins; apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthocyanins / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mice, Nude
  • NAD / metabolism
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • Receptors, Androgen / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Xenograft Model Antitumor Assays*
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • AR protein, human
  • Anthocyanins
  • Receptors, Androgen
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • NAD
  • Prostate-Specific Antigen