The Anti-tumor Effect of Quinazolinone Derivative Holu-12 on Oral Squamous Cell Carcinoma Cells

• Main Authors: CHIA, YI-TING, 賈貽婷
• Other Authors: LAI, KUO-CHU
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/99ecg4

碩士 === 慈濟大學 === 藥理暨毒理學碩士班/博士班 === 106 === Oral squamous cell carcinoma (OSCC) is one of the common malignant diseases in the world. Through advances in multimodality therapies for the treatment of OSCC; however, the overall 5-year survival rate for OSCC patients remains at 50% without significant improvement over the past three decades. Therefore, it is necessary to develop novel potential therapeutic agents against human OSCC. Quinazolinone is a heterocyclic chemical compound having a unique place in the field of medicinal chemistry. Many quinazolinone derivatives possess a wide range of bioactivities such as antimicrobial, anti-inflammatory, anticonvulsant, analgesic, anthelminthic and anticancer activities. In this study, we examined the therapeutic potential of 16 synthetic quinazolinone derivatives in OSCC by the sulforhodamine B (SRB) cytotoxicity assay. Among them, HoLu-12 exhibited no cytotoxicity toward the human normal oral mucosa fibroblast (OMF) cells. However, HoLu-12 significantly reduced the viability of several human OSCC cell lines, such as CAL27 and OECM-1. Cell cycle analysis revealed that HoLu-12 induced G2/M arrest and sub G1 phase in OSCC cells. Western blot analysis showed that treatment with HoLu-12 increased the expression of cleaved PARP, indicating that HoLu-12 could induce apoptosis pathway. Subcutaneous xenograft model was performed to demonstrate that HoLu-12 could significantly inhibit OSCC growth in vivo with negligible body weight loss. In addition, we observed that combined treatment with HoLu-12 and 5-flurouracil had a synergistic cytotoxic effect in OSCC cells. Taken together, these results suggest that HoLu-12 may have the therapeutic potential against human OSCC cells.