Anti-tumor effect of emodin on gynecological cancer cells

Cell Oncol (Dordr). 2015 Oct;38(5):353-63. doi: 10.1007/s13402-015-0234-8. Epub 2015 Jul 11.


Purpose: Although an anti-tumor effect of emodin has been reported before, its effect on human gynecological cancer cells has so far not been studied. Here, we assessed the effect of emodin on cervical cancer-derived (Hela), choriocarcinoma-derived (JAR) and ovarian cancer-derived (HO-8910) cells, and investigated the possible underlying molecular and cellular mechanisms.

Methods and results: The respective cells were treated with 0, 5, 10 or 15 μM emodin for 72 h. Subsequently, MTT and Transwell in vitro migration assays revealed that emodin significantly decreased the viability and invasive capacity of the gynecological cancer-derived cells tested. We found that emodin induced apoptosis and significantly decreased mitochondrial membrane potential and ATP release in these cells. We also found that emodin may exert its apoptotic effects via regulating the activity of caspase-9 and the expression of cleaved-caspase-3. Moreover, we found that emodin induced a cell cycle arrest at the G0/G1 phase, possibly through down-regulating the key cell cycle regulators Cyclin D and Cyclin E. Interestingly, emodin also led to autophagic cell death, as revealed by increased MAP LC3 expression, a marker of the autophagosome, and decreased expression of the autophagy regulators Beclin-1 and Atg12-Atg5. Finally, we found that the protein levels of both VEGF and VEGFR-2 were significantly decreased in emodin-treated cells, suggesting an anti-angiogenic effect of emodin on gynecological cancer-derived cells.

Conclusions: Our results suggest that emodin exhibits an anti-tumor effect on gynecological cancer-derived cells, possibly through multiple mechanisms including the induction of apoptosis and autophagy, the arrest of the cell cycle, and the inhibition of angiogenesis. Our findings may provide a basis for the design of potential emodin-based strategies for the treatment of gynecological tumors.

Keywords: Angiogenesis; Anti-tumor effect; Apoptosis; Autophagy; Cell cycle arrest; Emodin; Gynecological cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects*
  • Blotting, Western
  • Caspase 9 / metabolism
  • Cell Cycle Checkpoints / drug effects*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Emodin / pharmacology*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genital Neoplasms, Female / genetics
  • Genital Neoplasms, Female / metabolism
  • Genital Neoplasms, Female / pathology
  • HeLa Cells
  • Humans
  • Matrix Metalloproteinase 9 / genetics
  • Membrane Potential, Mitochondrial / drug effects
  • Microtubule-Associated Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Microtubule-Associated Proteins
  • Vascular Endothelial Growth Factor A
  • light chain 3, human
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Caspase 9
  • Matrix Metalloproteinase 9
  • Emodin