Oleanolic Acid Inhibits Aldo-keto Reductase Family 1 Member B10-induced Cancer Stemness and Avoids Cisplatin-based Chemotherapy Resistance Via the Snail Signaling Pathway in Oral Squamous Cell Carcinoma Cell Lines

Overview

Journal J Dent Sci

Date 2025 Jan 28

PMID 39873100

Authors

Hui-Hsin Ko

Han-Yi E Chou

Hsin-Han Hou

Wei-Ting Kuo

Wei-Wen Liu

Mark Yen-Ping Kuo

Shih-Jung Cheng

Affiliations

Soon will be listed here.

Abstract

Background/purpose: Oral squamous cell carcinoma (OSCC) is a common malignancy often associated with poor prognosis due to chemoresistance. In this study, we investigated whether arecoline, a major alkaloid in betel nuts, can stimulate aldo-keto reductase family 1 member B10 (AKR1B10) levels in OSCC, promoting cancer stemness and leading to resistance to cisplatin (CDDP)-based chemotherapy.

Materials And Methods: Gain- and Loss- of AKR1B10 functions were analyzed using WB and q-PCR of OSCC cells. Stemness, epithelial mesenchymal transition (EMT) markers, and CDDP drug resistance in overexpressed AKR1B10 were also identified.

Results: Upregulated AKR1B10 in OSCC significantly increased cell motility and aggregation. The results also showed that the canonical TGF-β1-Smad3 pathway was involved in arecoline-induced AKR1B10 expression, further increasing cancer stemness with CDDP resistance via the Snail-dependent EMT pathway. Moreover, oleanolic acid (OA) and ROS/RNS (reactive oxygen/nitrogen species) inhibitors effectively reversed AKR1B10-induced CDDP-resistance.

Conclusion: Arecoline-induced ROS/RNS to hyper-activate AKR1B10 in tumor sphere cells via the TGF-β1-Smad3 pathway. Furthermore, AKR1B10 enhanced CDDP resistance in OSCC cells via EMT-inducing markers. Finally, Finally, OA may efficiently target CDDP resistance, reverse stemness in OSCC cells, and have the potential as a novel anticancer drug.

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