Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 14, 2012; 18(2): 126-135
Published online Jan 14, 2012. doi: 10.3748/wjg.v18.i2.126
Suppression of esophageal cancer cell growth using curcumin, (-)-epigallocatechin-3-gallate and lovastatin
Fei Ye, Gui-Hong Zhang, Bao-Xiang Guan, Xiao-Chun Xu
Fei Ye, Gui-Hong Zhang, Bao-Xiang Guan, Xiao-chun Xu, Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Gui-Hong Zhang, Xiao-Chun Xu, Department of Pathology, Anhui Medical University, Hefei 230032, Anhui Province, China
Author contributions: Ye F, Zhang GH and Guan BX performed the experiments and data analysis; Xu XC designed the experiments, interpreted the data, and wrote the manuscript; Ye F and Zhang GH contributed equally to this work.
Supported by A United States National Cancer Institute Grant, No. R01 CA117895; and a grant from the Duncan Family Institute for Cancer Prevention and Risk Assessment, UT MD Anderson Cancer Center
Correspondence to: Dr. Xiao-Chun Xu, Department of Clinical Cancer Prevention, Unit 1360, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, United States. xxu@mdanderson.org
Telephone: +1-713-7452940 Fax: +1-713- 5635747
Received: May 24, 2011
Revised: July 28, 2011
Accepted: August 4, 2011
Published online: January 14, 2012

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: Chemoprevention, Curcumin, Cyclooxygenase-2, (-)-epigallocatechin-3-gallate, Esophageal cancer, Statin