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 plantSchisandra Chinensiswith 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..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 30. Nov. Zur Gesamtaufnahme - year:2022 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lee, Pui-Kei [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1101/2022.11.28.518277 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI038015056 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI038015056 | ||
| 003 | DE-627 | ||
| 005 | 20230429090534.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 221130s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2022.11.28.518277 |2 doi | |
| 035 | |a (DE-627)XBI038015056 | ||
| 035 | |a (biorXiv)10.1101/2022.11.28.518277 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lee, Pui-Kei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Bioavailability of Schisandrin B and its effect on 5-Fluorouracil metabolism in a xenograft mouse model of colorectal cancer |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Schisandrin B (Sch-B) is a predominant bioactive lignan in the fruit of a traditional Chinese medicinal plantSchisandra Chinensiswith 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. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Co, Vanessa Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Wan, Murphy Lam Yim |e verfasserin |4 aut | |
| 700 | 1 | |a El-Nezami, Hani |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Danyue |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2022) vom: 30. Nov. |
| 773 | 1 | 8 | |g year:2022 |g day:30 |g month:11 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2022.11.28.518277 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2022 |b 30 |c 11 | ||