Zymolytic grain extract facilitates the conversion of liver tumor cells to hepatocyte-like cells through hepatocyte nuclear factors

At present, malignant tumors are an urgent global threat to human health. Conversion of cancer cells to normal-like or normal cells will open new therapeutic avenues for eradicating cancer. It has been reported that compounds extracted from grains display biological activities, such as antioxidant, antiviral and antitumor activities. In this study, we identified clear changes in a liver tumor cell line (HepG2) after stimulation with zymolytic grain extract (ZGE) supernatants. The expression levels of hepatocyte nuclear factor 1A (HNF1A), hepatocyte nuclear factor 4A (HNF4A) and forkhead box protein A3 (FOXA3) were significantly increased. Eukaryotic transcriptome analyses revealed that trends in the transcriptional changes for genes were similar in HepG2 cells stimulated with ZGE (zHeps) and the normal hepatocyte cell line L02. Changes in the expression levels of genes involved in drug transport, metabolism and the malignant characteristics of cancer cells in nude mice further indicated that ZGE regulated the expression of HNF1A, HNF4A and FOXA3, which altered the expression of a series of hepatocyte-specific genes. It was also confirmed that zHeps acquired some of the characteristics of hepatocyte-like cells. Our results not only provide new ideas for the treatment of liver tumors but also lay a solid foundation for the application of combination therapy.