Effects of HYS-32 [4-(3,4-dimethoxyphenyl)-3-(naphthalen-2-yl)-2(5H)-furanone] on U87-MG Human Glioblastoma Cells

• Main Authors: Zong-Han Tsai, 蔡宗翰
• Other Authors: Jiahn-Chun Wu
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/55684924698197631927

碩士 === 國立陽明大學 === 解剖學及細胞生物學研究所 === 103 === Compound HYS-32 [4-(3,4-dimethoxyphenyl)-3-(naphthalen-2-yl)-2 (5H)-furanone] containing a cis-stilbene moiety is a new analogue of the antitumor compound combretastatin A-4 (CA-4). Glioblastoma multiforme (GBM) is the most aggressive malignant primary tumor in human brains. The effects of HYS-32 on GBM remain unknown. In this study, we investigated the effects of HYS-32 in the U87-MG human glioblastoma cell line and the signaling pathway involved. MTT assay demonstrated that HYS-32 causes a cytotoxic effect in U87-MG cells in a dose-dependent manner. Apo-Brdu-IHC in situ DNA fragmentation analysis and flow cytometry indicated cellular apoptosis and cell cycle arrest in U87-MG cells. Immunoblot analyses showed that HYS-32 induces a dose- and time-dependent increase in cytochrome c and cleaved caspase-3 protein levels, indicating cellular apoptosis in U87-MG cells. Moreover, immunoblot analyses also showed that HYS-32 induces a dose- and time-dependent increase in Beclin 1 and LC3-II protein levels but decrease in SQSTM1 levels, suggesting cellular autophagy in U87-MG cells. HYS-32 also induced aggregation of LC3 protein in cytoplasm, disassembly of microtubules, and morphology changes in U87-MG cells. Co-treatment of HYS-32 and Beclin 1 inhibitor Spautin 1 prevented the HYS-32-induced Beclin 1 upregulation and autophagy. Taken together, our results demonstrated that HYS-32 induces microtubule disassembly, cell cycle arrest, cellular apoptosis, and autophagy in U87-MG cells. The novel biological effects of HYS-32 on glioblastoma may become a new potential as a therapeutic drug used for treatment of human glioblastoma.