The Anti-tumor Activity Of CADPE And Its Potential Mechanism In Colorectal Cancer Cells

Colorectal cancer (CRC) is one of the most common malignancies and leading causes of cancer death. However, the drugs available now remain not yet satisfied because of their shortcomings. Hence, it is still meaningful to develop the new anti-tumor drugs. Therefore, the present study is aimed to demonstrate the anti-tumor activity of caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) and its potential mechanism in colorectal cancer cells. Methods:For in vitro study, the cell viabilities of colorectal cancer cells after treated with CADPE for 72 hours were determined by sulforhodamine B (SRB) assay. Flow cytometry and fluorescence microscope were used for testing the levels of ROS, cell cycle, apoptosis or necrosis, and mitochondrial membrane potential. In addition, western blot assays were also performed in order to test the expression or phosphorylation of proteins related to cell survival. For in vivo study, S180 sarcoma and H22 hepatoma model were performed to investigate the inhibitory effect on tumor growth of CADPE. Results:CADPE significantly suppressed the growth of multiple kinds of human colorectal cancer cells in a dose-dependent manner in vitro. CADPE also has anti-cancer effect in vivo on S180 sarcoma and H22 hepatoma model. CADPE treatment induced G1 and S arrest of HCT-15, which kept the cells in the G1 and S phage instead of entering the G2/M phage. Further study showed that incubation with CADPE decreased the expression of Cdc25A and the phosphorylation of Rb, while it increased phosphorylation of Cdc2 at Tyrl5 in SW620 cells, indicating that the down-regulation of Cdc25A may be involved in CADPE-induced cell cycle arrest. CADPE elevated ROS production and induced mitochondrial membrane depolarization, as well as cell apoptosis of tumor cells. Also, the expression of pro-apoptotic protein Bax was found to be increased in CADPE-treated SW620 cells. The activation of ERK1/2 and p38 was also found to be augmented by CADPE. CADPE had no obvious influence on the phosphorylated status of Chkl, Chk2, or JNK proteins in SW620 cells. Conclusions:Both in vitro and in vivo experiments showed the significant anti-tumor activity of CADPE in different tumor cells. CADPE treatment induced cell cycle arrest and apoptosis in colorectal cancer cells, as well as the down regulation of Cdc25A and inhibition of Cdc2. CADPE also increased intracellular ROS levels in colorectal tumor cells.