Anti-cancer Effect of Cyanidin-3-glucoside from Mulberry via Caspase-3 Cleavage and DNA Fragmentation in vitro and in vivo

Anticancer Agents Med Chem. 2017 Nov 24;17(11):1519-1525. doi: 10.2174/1871520617666170327152026.


Background: Fruits of Morus alba L. (mulberry) have various bioactive compounds such as polyphenols and anthocyanins and used as a herbal medicine. However, the anti-cancer effects and molecular basis have not been elucidated.

Methods: We isolated the cyanidin-3-glucoside in various cultivar of mulberry by acidified-methanol extraction methods. This molecule were compared mass spectroscopic properties by LC-MS/MS and analyzed by 1H and 13C NMR. We examined the anti-cancer effect with molecular mechanisms of the cyanidin-3-glucoside on MDA-MB-453 human breast cancer cells and xenograft animal model.

Results: The treatment with the mulberry cyanidin-3-glucoside decreased cell viability in a dose-dependent manner with alteration of apoptotic protein contents, and DNA fragmentation, suggesting that cells undergo apoptosis. Supporting the observations, Treatment with the cyanidin-3-glucoside showed active apoptosis by caspase-3 cleavage and DNA fragmentation through Bcl-2 and Bax pathway. Indeed, cyanidin-3-glucoside inhibits tumor growth in MDA-MB-453 cells-inoculated nude mice. Tumor growth of xenograft nude mouse was significantly reduced compared to the control group by the cyanidin-3-glucoside.

Conclusion: The data demonstrate that cyanidin-3-glucoside isolated from mulberry induced apoptosis in breast cancer (MDA-MB-453) cells, and therefore, has a potential as an anti-cancer agent. These results show that mulberry cyanidin-3-glucoside inhibit the proliferation and growth in vitro and in vivo model and, indicating the inhibition of tumor progression.

Keywords: Cyanidin-3-glucoside; DNA fragmentation; Morus alba L.; anti-cancer; caspase-3; mulberry; nude mice..

MeSH terms

  • Animals
  • Anthocyanins / chemistry
  • Anthocyanins / metabolism
  • Anthocyanins / pharmacology*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Caspase 3 / metabolism*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • DNA Fragmentation / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Glucosides / chemistry
  • Glucosides / metabolism
  • Glucosides / pharmacology*
  • Humans
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred ICR
  • Molecular Structure
  • Morus / chemistry*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured


  • Anthocyanins
  • Antineoplastic Agents, Phytogenic
  • Glucosides
  • cyanidin-3-O-beta-glucopyranoside
  • Caspase 3