1. Department of Otolaryngology-Head and Neck Surgery, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
2. School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
3. Cancer Center, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
4. Department of Neurology, National Cheng-Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
5. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
6. Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
7. Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
8. School of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
9. Department of Medical Research and Development, Chiayi Chang Gung Memorial Hospital, Chiayi, No 6, Sec. West, Jiapu Rd., Puzi-City, Chiayi County, 61363, Taiwan.
Objective: Natural products in diet have shown a potential role in the prevention and treatment of cancer. Ginger (Zingiber officinale Roscoe) is a great candidate because of its properties of anti-inflammatory, antioxidant, and anti-cancer, but little is known about its effect on head and neck cancer. 6-Shogaol is an active compound derived from Ginger. Thus, this study aimed to investigate the possible anticancer effects of 6-shogaol, a major ginger derivate, on head and neck squamous cell carcinomas (HNSCCs) and the underlying mechanisms.
Material and Methods: Two HNSCC cell lines, SCC4 and SCC25, were used in this study. Both SCC4 and SCC25 cells were kept as control or treated with 6-shogaol for 8 and 24 hours and then the cell apoptosis and cell cycle progression of treated cells were examined by PI and Annexin V-FITC double stain and flow cytometry analysis. The Cleaved caspase 3, phosphorylations of ERK1/2 and p38 kinases were examined by Western blot analysis.
Results: The results showed that 6-shogaol significantly initiated the G2/M phase arrest of the cell cycle and apoptosis to inhibit the survival of both cell lines. Moreover, these responses could be regulated by ERK1/2 and p38 signaling. And, finally, we also demonstrated that 6-shogaol could enhance the cytotoxicity of cisplatin in HNSCC cells.
Conclusion: Our data provided new insights to understand the potential pharmaceutical efficacy of a ginger derivate, 6-shogaol, in antagonizing HNSCC survival. The present study suggests that 6-shogaol is a potential novel candidate for anti-HNSCCs therapy.
Keywords: 6-shogaol, head and neck squamous cell carcinoma, apoptosis, ginger, p38 signaling, extracellular signal-regulated kinase, mammalian mitogen-activated protein kinases