Zhiyu Zhang 1 , 2 , Chunhao Yu 1 , 2 , Chun-Feng Zhang 1 , 2 , Xiao-Hui Wu 1 , 2 , Xiao-Dong Wen 1 , 2 , Samantha Anderson 1 , 2 , Wei Du 3 , Wei-Hua Huang 4 , Shao-Ping Li 5 , * , Chong-Zhi Wang 1 , 2 , * , Chun-Su Yuan 1 , 2 , 6
18 July 2014
Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A) is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects ( p < 0.01). Next, we characterized the compound’s growth inhibitory effects in human colorectal cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells were significantly inhibited in both a concentration- and time-dependent manner (both p < 0.01). The IC50 was approximately 5 µM for HCT-116 and 7 µM for SW-480 cells. OPT A significantly induced apoptosis and arrested the cell cycle at the G2/M phase. From further mechanism explorations, our data showed that OPT A significantly upregulated the expression of a cluster of genes, especially the tumor necrosis factor receptor family and caspase family, suggesting that the tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced apoptosis.