Apoptotic effect of hesperidin through caspase3 activation in human colon cancer cells, SNU-C4

Phytomedicine. 2008 Jan;15(1-2):147-51. doi: 10.1016/j.phymed.2007.07.061. Epub 2007 Sep 25.


Hesperidin, a known flavonoid constituent of citrus, reduces the proliferation of many cancer cells. The apoptotic effects of hesperidin on human colon cancer cells, SNU-C4, were determined at concentrations of 1-100 microM. At 100 microM, hesperidin reduced cell viability to 65.00+/-0.05% of control values in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell death induced by hesperidin showed apoptotic features in 4,6-diamidino-2-phenylindole (DAPI) staining and in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. Examination of the expression of apoptosis-regulating genes indicated that hesperidin treatment decreased the expression of B-cell CLL/lymphoma 2 (BCL2) mRNA, and increased the expression of BCL2-associated X protein (BAX). The expression and activity of the major apoptotic factor caspase3 (CASP3) was increased significantly with hesperidin treatment. Hesperidin down-regulated the protein expression of pro-CASP3, and up-regulated the level of active CASP3. Thus, these results suggest that hesperidin could induce apoptosis in human colon cancer cells through CASP3 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Caspase 3 / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Citrus / chemistry
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hesperidin / chemistry
  • Hesperidin / pharmacology*
  • Humans
  • Molecular Structure
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / metabolism
  • bcl-2-Associated X Protein / genetics


  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • Hesperidin
  • Caspase 3