Overexpression of Histidine Decarboxylase Promotes Cancer Cell Apoptosis and Migration in Hn5 Cells Publisher Pubmed

Summary: Can HDC expression hold the key to better OSCC outcomes? Research suggests higher histidine decarboxylase levels improve survival but may boost tumor cell migration. #OSCC #CancerResearch

Yousefi T ; Shahsavari Z ; Derakhshan S ; Lashkarbolouki T ; Rajabibazl M ; Goudarzi A
Source: Naunyn-Schmiedeberg's Archives of Pharmacology Published:2026

Abstract

This study aimed to assess the expression of histidine decarboxylase (HDC) in oral squamous cell carcinoma (OSCC) and investigate its functional role in patient prognosis as well as in apoptosis and migration of OSCC cells. A total of 58 formalin-fixed, paraffin-embedded OSCC tissue samples were examined to analyze the correlation between HDC expression levels and overall patient survival. Further, the effects of HDC modulation were studied in vitro using the HN5 cell line. Histidine, phorbol 12-myristate 13-acetate (PMA), quercetin, and their combinations with histidine were used to alter HDC expression level. The resulting changes in cell proliferation, apoptosis, migration, the expression of matrix metalloproteinases (MMP2, MMP7, MMP9), and histamine receptors were assessed using the MTT assay, flow cytometry, wound healing assay, and RT-qPCR. Immunohistochemistry data showed that patients with low HDC expression had significantly poorer overall survival compared to those with high HDC expression. In vitro findings showed that combined treatment of histidine and PMA significantly increased HDC expression level beyond the levels observed with each agent alone. Co-treatment of histidine + PMA also caused a notable increase in apoptosis. However, it simultaneously promoted cell migration and upregulated the expression of MMP2, MMP7, and MMP9. These results suggest that while HDC overexpression may contribute to improved prognosis in OSCC by promoting apoptosis, its concurrent role in enhancing tumor cell migration presents a paradox that requires further investigation. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.