The bound polyphenols of foxtail millet (Setaria italica) inner shell inhibit breast cancer by promoting lipid accumulation-induced autophagic death.

Foxtail millet is a traditional excellent crop with high nutritional value in the world, belong to cereals. The bran of foxtail millet is rich in polyphenol that has antioxidant, anti-inflammatory, and anti-tumorigenic effects. Previously, we extracted bound polyphenols from the inner shell of foxtail millet bran (BPIS). Here, we report that BPIS specifically induced breast cancer cell death and elevated the autophagy level simultaneously. The addition of an autophagy inhibitor blocked BPIS-induced breast cancer cell death, indicating that excessive autophagy induced cell death. Furthermore, oil red O and BODIPY staining also confirmed that lipids, which are important inducers of autophagy, accumulated in breast cancer cells treated with BPIS. Lipidomics research revealed that glycerophospholipids were the main accumulated lipids induced by BPIS. Further study showed that elevated PCYT1A expression was responsible for glycerophospholipid accumulation, and BPIS contained ferulic acid and p-coumaric acid, which induced PCYT1A expression and breast cancer cell death. Collectively, our results revealed that BPIS resulted in autophagic death by enhancing lipid accumulation in breast cancer cells, and BPIS contains ferulic acid and p-coumaric acid, which provided new insights into developing nutraceuticals and drugs for breast cancer patients.

The potential mechanism of Neu5Gc inducing colorectal cancer based on network pharmacology and experimental validation.

Colorectal cancer has high morbidity and mortality worldwide, especially in western countries; the incidence of colorectal cancer has been high, which is closely related to the high intake of red meat; and the N-glycolylneuraminic acid (Neu5Gc) is responsible for red meat-induced colorectal cancer. A large number of previous studies have suggested that exogenous Neu5Gc-activated inflammation induced the occurrence of colorectal cancer. However, it has not been known whether the Neu5Gc has a direct inducing effect on colorectal cancer. In this study, we found that Neu5Gc promoted the proliferation of colorectal cancer cells and normal intestinal epithelial cells, and further screened out 98 Neu5Gc targets related to the occurrence and development of colorectal cancer by network pharmacology. Subsequently, GO and KEGG enrichment analyses of these targets revealed that mainly enriched in the PI3K-Akt signaling pathway. Then, we selected SRC, HRAS, CDK2, CCNA2, and AKT2 as core targets based on the phenomena of the previous experiments and the available literature reports, and then we used AutoDock for molecular docking with Neu5Gc; the results found that these five genes could bind to Neu5Gc stably. In vitro experiments showed that the mRNA levels of SRC, HRAS, AKT2, CDK2, and CCNA2 were upregulated and the protein levels of HRAS, AKT2, and CCNA2 were enhanced in FHC and SW620 cells after Neu5Gc (100 ng/mL) treatment. In conclusion, this study revealed that Neu5Gc probably acted as a carcinogen that stimulates the expression of proto-oncogene HRAS and the PI3K-Akt pathway and accelerated cell cycle progression. These findings revealed a novel mechanism that Neu5Gc promoted the occurrence and development of colorectal cancer.