Sinapic Acid Reduces Hypoxia-Induced Cell Damage in Hep-2 Cells by Regulating TRPM2 Channel Activation
Journal of Biochemical and Molecular Toxicology, cilt.40, sa.7, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 40 Sayı: 7
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/jbt.70977
- Dergi Adı: Journal of Biochemical and Molecular Toxicology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, Environment Index, MEDLINE, Zoological Record, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Anahtar Kelimeler: calcium signaling, hypoxia, laryngeal squamous cell, sinapic acid, TRPM2 channel
- Van Yüzüncü Yıl Üniversitesi Adresli: Evet
Özet
Hypoxia (HPX) is a significant pathological factor that contributes to mitochondrial dysfunction, oxidative stress, inflammation, and calcium dysregulation in laryngeal squamous cell carcinoma (LSCC). The redox-sensitive TRPM2 channel is crucial for mediating HPX-induced Ca2+ excess and subsequent cell death. This study investigated whether sinapic acid (SPA), a natural phenolic compound with known antioxidant and anti-inflammatory properties, can protect Hep-2 cells from HPX-induced injury by modulating TRPM2 activity. Hep-2 cells were exposed to CoCl2-induced HPX and treated with SPA (10–150 μM). Cell viability, oxidative stress parameters (malondialdehyde [MDA], glutathione [GSH], and reactive oxygen species [ROS]), intracellular Ca2+ levels, mitochondrial membrane potential, and pro-inflammatory cytokines (IL-1β and TNF-α), TRPM2 expression, and PI-positive cell death were evaluated. HPX markedly decreased cell viability and increased oxidative and inflammatory responses, mitochondrial depolarization, and TRPM2-dependent Ca2+ influx. SPA significantly restored GSH levels, reduced MDA and ROS accumulation, suppressed cytokine production, and stabilized mitochondrial membrane potential. Moreover, SPA attenuated TRPM2 upregulation and effectively lowered Ca2+ overload. Co-treatment with the widely used TRPM2 channel inhibitor 2-APB further enhanced SPA's protective effects and produced the greatest reduction in cell death. These findings demonstrate that SPA mitigates HPX-induced cytotoxicity through antioxidative, anti-inflammatory, and TRPM2-modulating mechanisms, highlighting its potential therapeutic relevance in LSCC.