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Sulindac sulfide-induced apoptosis in sinonasal cancer cells
Chang-Hoon Kim1, Kyoung Seob Song, Kyung-Su Kim
1Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea.
Conclusions:
These results demonstrate that sulindac sulfide can induce cell death in maxillary cancer cells, and that sulindac sulfide-induced apoptosis is related to the extracellular signal-regulated kinase/p38 MAPK-caspase 3 signaling pathway.
Objective:
Head and neck cancer is the sixth commonest cancer in the human body. Squamous cell carcinoma accounts for most sinonasal cancers. However, little is known regarding the biochemical mechanism(s) of cell death in sinonasal cancers. Recently, human epidemiological and clinical intervention studies have indicated that sulindac, a non-steroidal anti-inflammatory drug, exhibits chemopreventive activity in colorectal cancer. In this study, we aimed to investigate whether sulindac sulfide can induce apoptosis in sinonasal cancer cells and what type of molecular mechanisms induces the death of sinonasal cancer cells.
Material And Methods:
Sinonasal cancer cells (Asan Medical Center Head and Neck Cancer 5) were treated with various concentrations of sulindac sulfide. The degree of cell death was determined by means of a fluorescence-activated cell scan and the signal transduction pathway for cell death was examined.
Results:
Human nasal cavity cancer cells treated with sulindac sulfide underwent cell death, and the induction of apoptosis occurred in a dose-dependent manner. Moreover, sulindac sulfide-induced apoptosis was abolished by treatment with the caspase inhibitor Z-VAD-fmk and the mitogen-activated protein kinase (MAPK) inhibitors PD98059 and SB203580.
Insights
Sulindac sulfide induces apoptosis in sinonasal cancer cells via the extracellular signal-regulated kinase/p38 mitogen-activated protein kinase (MAPK) and caspase-3 pathway. This finding offers potential therapeutic insights for head and neck cancers.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Head and neck cancers, particularly sinonasal squamous cell carcinoma, lack well-defined cell death mechanisms.
- Non-steroidal anti-inflammatory drugs, like sulindac, show chemopreventive potential in colorectal cancer.
Purpose of the Study:
- To investigate sulindac sulfide's apoptosis-inducing effects on sinonasal cancer cells.
- To elucidate the molecular pathways involved in sulindac sulfide-mediated cell death.
Main Methods:
- Sinonasal cancer cells were exposed to varying concentrations of sulindac sulfide.
- Cell death was quantified using fluorescence-activated cell scanning.
- Signal transduction pathways were analyzed using specific kinase and caspase inhibitors.
Main Results:
- Sulindac sulfide induced apoptosis in sinonasal cancer cells in a dose-dependent manner.
- Apoptosis was significantly reduced by caspase inhibitor Z-VAD-fmk.
- Mitogen-activated protein kinase (MAPK) inhibitors (PD98059 and SB203580) also blocked sulindac sulfide-induced apoptosis.
Conclusions:
- Sulindac sulfide effectively induces apoptosis in maxillary cancer cells.
- The observed apoptosis is mediated through the extracellular signal-regulated kinase/p38 MAPK-caspase 3 signaling pathway.