Anti-CA9 monoclonal antibody, clone 3E4

Ellagitannin oligomers are large molecules habitually showing complex NMR spectra that are sometimes misinterpreted and lead to incorrect structures. Understanding the NMR spectroscopic features of a group of ellagitannins would overcome these inadequacies. In this study, investigation of the galls of Tamarix aphylla led to the isolation of three new ellagitannin oligomers, phyllagallins T1 (1), T2 (2), and Q1 (3), a known monomer nilotinin M4 (4), four known dimers, nilotinins D7 (5) and D8 (6), hirtellin B (7), and tamarixinin A (8), and a simple phenolic, dehydrotrigallic acid (9). 1D and 2D NMR, HRESI-TOFMS, and ECD experiments show that compounds 1-8 are hellinoyl-type ellagitannins. The NMR spectroscopic features of this type of ellagitannins and the reasons for the abnormal upfield shifts of glucose anomeric proton and hellinoyl moiety proton signals are established considering the experimental results as well as quantum chemical calculation on a simple hellinoyl-type monomer, phyllagallin M2. Based on these results, the NMR assignments reported previously by a different research group for bracteatinin T-1 and hirtellin T-3 are revised. A cytotoxicity study against human oral squamous cell carcinoma cell lines (Ca9-22, HSC-2, and HSC-4) and human mesenchymal normal oral cells (HGF, HPC, and HPLF) showed cytotoxic effects with tumor-specificity higher than 5.2, 3.0, 1.6, and 2.0 for compounds 5, 2, 9, and 3, respectively.

Fisetin (3,3-,4-,7-tetrahydroxyflavone), a naturally occurring flavonoid, has antioxidant, anti-inflammatory, and anticancer effects. Oral squamous cell carcinoma (OSCC) has a 5-year survival rate lower than that of most other carcinomas, and can create functional and aesthetic problems for the patient. New therapies for OSCC are necessary, and treatment using plant-derived natural substances has recently become a trend. It has been suggested that autophagy may play an important role in cancer therapy. Several studies demonstrated that autophagy inhibition enhances apoptotic cell death. Therefore, autophagy inhibition might be a promising therapeutic method against OSCC. Our results showed that fisetin induced apoptotic cell death in human tongue squamous cell line Ca9-22 could be enhanced by inhibition of autophagy. Thus, autophagy process in fisetin treated OSCC might presumed to play a role of pro-survival. The combination of fisetin and an effective autophagy inhibitor could be a potentially adjuvant and useful treatment for oral cancer.