Bufalin Suppresses Head and Neck Cancer Development by Modulating Immune Responses and Targeting the β-Catenin Signaling Pathway

Author:

Mhaidly Nour1,Barake Noura1,Trelcat Anne1,Journe Fabrice2ORCID,Saussez Sven1ORCID,Descamps Géraldine1ORCID

Affiliation:

1. Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, Research Institute for Health Sciences and Technology, University of Mons, Avenue du Champ de Mars, 8, 7000 Mons, Belgium

2. Laboratory of Clinical and Experimental Oncology (LOCE), Institute Jules Bordet, Université Libre de Bruxelles (ULB), 1000 Brussels, Belgium

Abstract

Bufalin, a cardiotonic steroid derived from the Chinese toad (Bufo gargarizans), has demonstrated potent anticancer properties across various cancer types, positioning it as a promising therapeutic candidate. However, comprehensive mechanistic studies specific to head and neck cancers have been lacking. Our study aimed to bridge this gap by investigating bufalin’s mechanisms of action in head and neck cancer cells. Using several methods, such as Western blotting, immunofluorescence, and flow cytometry, we observed bufalin’s dose-dependent reduction in cell viability, disruption of cell membrane integrity, and inhibition of colony formation in both HPV-positive and HPV-negative cell lines. Bufalin induces apoptosis through the modulation of apoptosis-related proteins, mitochondrial function, and reactive oxygen species production. It also arrests the cell cycle at the G2/M phase and attenuates cell migration while affecting epithelial–mesenchymal transition markers and targeting pivotal signaling pathways, including Wnt/β-catenin, EGFR, and NF-κB. Additionally, bufalin exerted immunomodulatory effects by polarizing macrophages toward the M1 phenotype, bolstering antitumor immune responses. These findings underscore bufalin’s potential as a multifaceted therapeutic agent against head and neck cancers, targeting essential pathways involved in proliferation, apoptosis, cell cycle regulation, metastasis, and immune modulation. Further research is warranted to validate these mechanisms and optimize bufalin’s clinical application.

Funder

F.R.S.-FNRS-Télévie

Walloon Region via the ProtherWal Society

The confocal microscope Nikon Ti2

Publisher

MDPI AG

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