Stevioside induced ROS-mediated apoptosis through mitochondrial pathway in human breast cancer cell line MCF-7

Nutr Cancer. 2012;64(7):1087-94. doi: 10.1080/01635581.2012.712735.


Stevioside is a diterpene glycoside found in the leaf of Stevia rebaudiana, a traditional oriental medicinal herb, which has been shown to have various biological and ethno-medicinal activities including antitumor activity. In this study, we investigated the effects of stevioside on the cytotoxicity, induction of apoptosis, and the putative pathways of its action in human breast cancer cells (MCF-7). For the analysis of apoptotic pathway, measurement of reactive oxygen species (ROS) and assessment of mitochondrial transmembrane potential (MTP) were achieved. We showed that stevioside was a potent inducer of apoptosis and it conveyed the apoptotic signal via intracellular ROS generation; thereby inducing change in MTP and induction of mitochondrial mediated apoptotic pathway. Taken together, our data indicated that stevioside induces the ROS-mediated mitochondrial permeability transition and results in the increased expression of apoptotic proteins such as Bax, Bcl-2 and Caspase-9. Effect of stevioside on stress-related transcription factors like NF-E2-related factor-2 opens up a new vista for further studies. This is the first report on the mechanism of the antibreast cancer (in vitro) activity of stevioside.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Blotting, Western
  • Breast Neoplasms / pathology
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Diterpenes, Kaurane / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Glucosides / pharmacology*
  • Humans
  • MCF-7 Cells
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • NF-E2-Related Factor 1 / genetics
  • NF-E2-Related Factor 1 / metabolism
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • Diterpenes, Kaurane
  • Glucosides
  • NF-E2-Related Factor 1
  • NFE2L1 protein, human
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • stevioside
  • CASP9 protein, human
  • Caspase 9