Epigallocatechin gallate stimulated histamine production and downregulated histamine H1 receptor in oral cancer cell lines expressing histidine decarboxylase

Abstract

Objectives: Increased histamine production and the overexpression of receptors (H1R∼H4R) has been reported in several tumors. The effects of TGFβ1 and epigallocatechin gallate (EGCG) on histamine synthesizing enzymes (HDCs), and the histamine transporter systems and receptors were investigated in this study.

Methods: Four oral cancer cell lines (HSC2, HSC3, HSC4, and SAS) were treated with or without TGFβ1 or EGCG for 24 h. The expression levels of HDC, SLC22A3, H1R∼H4R, and TAS2R14 were investigated by Western blotting. Histamine concentrations were determined using the enzyme immune assay. Bitter taste receptor (TAS2R14 and TAS2R39) mRNAs were investigated by RT-PCR.

Results: Varying expression levels of HDC, SLC22A3, H1R∼H4R, and TAS2R14 were observed in the four cell lines, where histamine concentrations were found to be ∼500 fmol/ml in cell culture media and induced 2-2.5 times higher amounts of histamine following EGCG treatment. TGFβ1 increased HDC expression in three cell lines, SLC22A3 expression in three cell lines, H1R expression in two cell lines, H2R expression in three cell lines, H3R expression in three cell lines, and H4R expression in three cell lines. EGCG decreased HDC expression in all four cell lines, SLC22A3 expression in three expression, H1R expression in all four cell lines, H2R expression in two cell lines, H3R expression in three cell lines, and H4R expression in two cell lines.

Conclusions: EGCG upregulated histamine production and decreased the expression level of H1R in the oral cancer cell lines. It might prove useful for cancer therapy during histamine regulation.

Keywords: Epigallocatechin gallate (EGCG); Histamine; Histamine receptors; Oral squamous cell carcinoma; solute carrier 22A3.