Abstract
Background: Esophageal cancer responds poorly to traditional therapies, and novel treatments are needed. The phytochemical curcumin is a potential treatment for Esophageal Squamous Cell Carcinoma (ESCC). A curcumin metabolite, tetrahydrocurcumin (THCUR), has anti-cancer effects and greater bioavailability than curcumin.
Objective: Evaluate THCUR as an anti-cancer agent relative to curcumin and a standard cancer drug, 5-fluorouracil (5-FU), along with treatment interactions.
Materials and Methods: Assay cell proliferation and viability following individual and combined delivery of the compounds to three ESSC cell lines (TE-1, TE-8, and KY-5) that have different percentages of Cancer Stem Cells (CSCs).
Results: Curcumin was significantly more effective than 5-FU in all three cell lines. It also had the greatest effect on KY-5 cells, which have the highest CSC properties, consistent with the ability of curcumin to target CSCs. Effects on ESCC cell proliferation were not detected from 40µM THCUR, a dosage above the IC50 of curcumin and 5-FU. However, THCUR at this dosage in combination with 5-FU significantly suppressed TE-1 cell proliferation, but 5-FU alone did not. As TE-1 has low CSC properties relative to the two other cell lines, it was expected to have the least resistance to chemotherapeutic treatments. Surprisingly, TE-1 was the most resistant to inhibition by 5-FU.
Conclusion: These results and the greater stability and water solubility of THCUR than curcumin support further testing of THCUR in combination with standard treatments, particularly for chemoresistant ESCC. In contrast to concerns that curcuminoids taken by patients through diet or diet supplements might interfere with chemotherapy, suppression of 5-FU efficacy by curcumin was not observed.
Keywords: Tetrahydrocurcumin, curcumin, esophagus, cancer stem cell, chemoresistance, drug interactions.
Graphical Abstract
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