Bioavailability of Schisandrin B and its effect on 5-Fluorouracil metabolism in a xenograft mouse model of colorectal cancer

Abstract

Schisandrin B (Sch-B) is a predominant bioactive lignan in the fruit of a traditional Chinese medicinal plant Schisandra Chinensis with widely reported anti-cancer properties. Using a xenograft mouse model of colorectal cancer (CRC), we showed potent anti-tumor effects of Sch-B and synergistic effects when co-treated with the chemotherapy drug, fluorouracil (5-FU). To explore the underlying anti-tumor mechanism of Sch-B, we first compared the bioavailability, metabolism and tissue distribution of Sch-B and its metabolites among healthy and tumor-bearing mice. To understand the drug-phytochemical interactions associated with the synergy between Sch-B and 5-FU, we examined their reciprocal influence on drug metabolism, tissue distribution, and multidrug resistance (MDR) gene expression in tumor-bearing mice. Using a targeted metabolomics approach, three Sch-B metabolites and two bioactive 5-FU metabolites were quantified and found to reach tumor tissue. Generally, Sch-B metabolites were present at higher levels in tumor-bearing than healthy mice, whereas 5-FU metabolite accumulation was remarkably higher in the co-treatment than 5-FU alone group. Moreover, MDR genes were significantly downregulated upon co-treatment, demonstrating the capacity of Sch-B to reverse MDR in chemotherapy. This study showed that Sch-B may serve as a promising adjuvant to chemotherapy drugs via favorably modulating drug metabolism and bioavailability, and attenuating MDR.

Inhibition of autophagy enhances the anticancer effect of Schisandrin B on head and neck squamous cell carcinoma

“…[ 20 ] For example, in colorectal cancer, Sch‐B can act synergistically with the 5‐fluorouracil by favorably modulating drug metabolism and bioavailability, and attenuating multidrug resistance. [ 21 ] The low toxicity of Sch B, its reversal of drug resistance and its inhibitory effect on tumor cells make it a very valuable adjuvant drug in the clinical treatment of tumors. However, the effect and mechanism of Sch B on HNSCC cells have not been studied.…”