Colon cancer chemopreventive effects of baicalein, an active enteric microbiome metabolite from baicalin

Abstract

Baicalin is a major constituent of Scutellaria baicalensis, which is a commonly used herbal medicine in many Asian countries. After oral ingestion, intestinal micro-biota metabolism may change parent compound's structure and its biological activities. However, whether baicalin can be metabolized by enteric microbiota and the related anti-cancer activity is not clear. In this study, using human enteric microbiome incubation and HPLC analysis, we observed that baicalin can be quickly converted to baicalein. We compared the antiproliferative effects of baicalin and baicalein using a panel of human cancer cell lines, including three human colorectal cancer (CRC) cell lines. In vitro antiproliferative effects on CRC cells were verified using an in vivo xenograft nude mouse model. Baicalin showed limited antiproliferative effects on some of these cancer cell lines. Baicalein, however, showed significant antiproliferative effects in all the tested cancer cell lines, especially on HCT-116 human colorectal cancer cells. In vivo antitumor results supported our in vitro data. We demonstrated that baicalein exerts potent S phase cell cycle arrest and pro-apoptotic effects in HCT-116 cells. Baicalein induced the activation of caspase 3 and 9. The in silico modeling suggested that baicalein forms hydrogen bonds with residues Ser251 and Asp253 at the active site of caspase 3, while interactions with residues Leu227 and Asp228 in caspase 9 through its hydroxyl groups. Data from this study suggested that baicalein is a potent anticancer metabolite derived from S. baicalensis. Enteric microbiota play a key role in the colon cancer chemoprevention of S. baicalensis.

The Fascinating Effects of Baicalein on Cancer: A Review

“…These results also indicated that baicalein-induced apoptosis is mediated through Akt activation in a p53-dependent manner [37]. Baicalein treatment also arrested the cell cycle at the S phase of division and promoted apoptosis in human colorectal adenocarcinoma cells (HCT116 cells) via the activation of caspase-3 and -9 [38]. Another study reported that baicalein inhibited the growth of HCT116 cells and induced cellular apoptosis.…”

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin

“…Baicalein is an active metabolite of enteral microbiome extracted from baicalin, which is a major ingredient of Scutellaria baicalensis as an herbal medicine commonly used in many Asian countries [12]. Combination of baicalein and other natural products can effectively modulate colorectal tumorigenesis.…”

“…Beyond that, the activation of the AMPK/ULK1 pathway induced by baicalein is associated with a variety of human cancers [11]. Wang CZ et al investigated the chemopreventive effects of baicalein in colon cancer and verified its significant antiproliferative effects on colon cancer cells in in vitro and in vivo assays [12]. However, the underlying molecular mechanisms of baicalein in CRC remain to be further elucidated.…”

Lung-targeting drug delivery system of baicalin-loaded nanoliposomes: development, biodistribution in rabbits, and pharmacodynamics in nude mice bearing orthotopic human lung cancer

“…6,7 Extensive studies have shown that baicalin has strong antitumor effects. [8][9][10] For the treatment of lung cancer, in vitro experiments, baicalin could suppress cell proliferation of human lung cancer A549 and mouse Lewis lung cancer in a dose-and time-dependent behavior. In in vivo study, baicalin could reduce tumor growth and prolong survival period in C57BL/6 mice bearing Lewis lung carcinoma tumor and nude mice bearing A549 carcinoma.…”