Suppression of esophageal cancer cell growth using curcumin, (-)-epigallocatechin-3-gallate and lovastatin

World J Gastroenterol. 2012 Jan 14;18(2):126-35. doi: 10.3748/wjg.v18.i2.126.


Aim: To determine the effects of curcumin, (-)-epigallocatechin-3-gallate (EGCG), lovastatin, and their combinations on inhibition of esophageal cancer.

Methods: Esophageal cancer TE-8 and SKGT-4 cell lines were subjected to cell viability methyl thiazolyl tetrazolium and tumor cell invasion assays in vitro and tumor formation and growth in nude mouse xenografts with or without curcumin, EGCG and lovastatin treatment. Gene expression was detected using immunohistochemistry and Western blotting in tumor cell lines, tumor xenografts and human esophageal cancer tissues, respectively.

Results: These drugs individually or in combinations significantly reduced the viability and invasion capacity of esophageal cancer cells in vitro. Molecularly, these three agents reduced the expression of phosphorylated extracellular-signal-regulated kinases (Erk1/2), c-Jun and cyclooxygenase-2 (COX-2), but activated caspase 3 in esophageal cancer cells. The nude mouse xenograft assay showed that EGCG and the combinations of curcumin, EGCG and lovastatin suppressed esophageal cancer cell growth and reduced the expression of Ki67, phosphorylated Erk1/2 and COX-2. The expression of phosphorylated Erk1/2 and COX-2 in esophageal cancer tissue specimens was also analyzed using immunohistochemistry. The data demonstrated that 77 of 156 (49.4%) tumors expressed phosphorylated Erk1/2 and that 121 of 156 (77.6%) esophageal cancers expressed COX-2 protein. In particular, phosphorylated Erk1/2 was expressed in 23 of 50 (46%) cases of esophageal squamous cell carcinoma (SCC) and in 54 of 106 (50.9%) cases of adenocarcinoma, while COX-2 was expressed in 39 of 50 (78%) esophageal SCC and in 82 of 106 (77.4%) esophageal adenocarcinoma.

Conclusion: The combinations of curcumin, EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts, these drugs also inhibited phosphorylated Erk1/2, c-Jun and COX-2 expression.

Keywords: (-)-epigallocatechin-3-gallate; Chemoprevention; Curcumin; Cyclooxygenase-2; Esophageal cancer; Statin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Anticarcinogenic Agents / therapeutic use*
  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Catechin / therapeutic use
  • Cell Line, Tumor / drug effects
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / pharmacology
  • Cyclooxygenase Inhibitors / therapeutic use
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology*
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression / drug effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lovastatin / pharmacology
  • Lovastatin / therapeutic use*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Transplantation, Heterologous


  • Anticarcinogenic Agents
  • Anticholesteremic Agents
  • Cyclooxygenase Inhibitors
  • Catechin
  • Lovastatin
  • epigallocatechin gallate
  • Cyclooxygenase 2
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Curcumin