Apigenin suppresses the growth of colorectal cancer xenografts via phosphorylation and up-regulated FADD expression.

ABSTRACT

Apigenin is a flavonoid belonging to the flavone structural class. It has been implicated as a chemopreventive agent against prostate and breast cancers. However, to the best of our knowledge, no published data are available regarding apigenin in colorectal cancer (CRC). The effects and mechanisms of apigenin on CRC may vary significantly. This study aimed to analyze the effects of apigenin on the growth of CRC xenografts in nude mice derived from SW480, as well as to investigate the underlying mechanisms. Whole-body fluorescence imaging is an inexpensive optical system used to visualize gene expression in small mammals using reporter genes, such as eGFP as a reporter. In our study, the expression of eGFP may reflect the size of the tumor. A terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay showed that apigenin promoted the apoptosis of CRC cells. Furthermore, the expression of five genes related to the proliferation and apoptosis of CRC, i.e., cyclin D1, BAG-1, Bcl-2, yrdC and Fas-associated protein with death domain (FADD), was detected by real-time quantitative RT-PCR. Among these genes, the up-regulated expression of FADD was noted in CRC xenograft tumors treated with apigenin. Immunohistochemistry and Western blotting confirmed the results at the protein level. Furthermore, Western blot analysis showed that apigenin induced the phosphorylation of FADD. Our findings suggest that apigenin enhances the expression of FADD and induces its phosphorylation, which may cause apoptosis of CRC cells and inhibition of tumor growth.