Three phytosterols from sweet potato inhibit MCF7-xenograft-tumor growth through modulating gut microbiota homeostasis and SCFAs secretion

Abstract

Researches demonstrated that gut microbiota are associated with breast cancer progression. This study aims to evaluate the anti-breast tumor effects of daucosterol linolenate (DLA), daucosterol linoleate (DL), and daucosterol palmitate (DP) from sweet potato in MCF-7 xenograft nude mice by determining the tumor growth, serum tumor markers, tumor-related proteins, and performing 16S rDNA sequencing. After treatment at 87.8 mg/kg/day for 29 days, DLA, DL and DP delayed tumor growth and decreased levels of tumor marker carcinoembryonic antigen (CEA), cancer antigen 125 (CA125) and cancer antigen 153 (CA153) in vivo. All treatments activated caspase 3, 9, PARP1 cleavage, down-regulated Ki67, VEGF, BCL-2, BCL-XL, up-regulated BAX expression, and inhibited PI3K/AKT/NF-κB activation in tumor tissues. Their anti-breast tumor effects were associated with the regulation on gut microbiota. The three treatments increased Bacteroidetes whereas decreased Firmicutes richness. They also modulated the diversity of gut microbiota at family and genus levels. Furthermore, DL treatment promoted butyric acid secretion, DP promoted acetic acid and butyric acid secretion in the colorectal and feces. Our findings indicate that DLA, DL, and DP inhibit tumor growth in MCF-7 xenograft nude mice by regulating the homeostasis of gut microbiota, producing SCFAs, and then disturbing the expression of cancer-related proteins. The present study suggests three phytosterols as gut microbiota regulator for breast cancer prevention.

Keywords: Breast cancer; Gut microbiota; MCF-7 xenograft; Phytosterol; Short chain fatty acid.