Interaction of quercetin and 5-fluorouracil: cellular and pharmacokinetic study

Abstract

5-fluorouracil (5-FU) is a widely used chemotherapeutic agent, and its uncontrolled blood levels contribute to toxicity. Quercetin, as an important flavonoid, has many biological effects, including anti-tumor and anti-inflammatory features. The current study investigated the synergistic effect between 5-FU and quercetin using HT-29 cell line and fibroblast cells. Rats were assigned to two groups. The 5-FU/quercetin group received intraperitoneal quercetin (10 mg/kg) and the Tween was injected to the control group for 14 consecutive days. On the 15th day, both groups received 50 mg/kg of 5-FU. Upon the final injection, blood samples were obtained at different times. Pharmacokinetic parameters were evaluated using high-performance liquid chromatography (HPLC). The mean (±SD) of maximum plasma concentration (C_max) of 5-FU in combination therapy group was 3.10 ± 0.18 μg/ml and the area under the curve (AUC) was 153.89 ± 21.36, which increased by 113% and 128% compared to control group, respectively. Quercetin increased anti-tumor activity of 5-FU and enhanced C_max and AUC of 5-FU. These findings confirm the synergistic effects between quercetin and 5-FU at the usual doses in cancer treatment, which may lead to reduced toxicity.

Graphical Abstract

Graphical abstract of the procedures and assessments performed in this article. Created with BioRender.com.

Keywords:

• Quercetin
• flavonoids
• 5-fluorouracil
• HT-29
• pharmacokinetics

Acknowledgment

This research was funded by the research affairs division of the Babol University of Medical Sciences.

Ethical approval

This study was approved by the Ethics Committee of Islamic Azad University, Ayatollah Amoli Branch (IR.IAU.AMOL.REC.1399.465).

Author contributions

AAM and SK conceptualized the study. ATP prepared the initial draft of the paper. RM & ME and SK revised and edited the manuscript. AAA & SA conducted the statistical tests. SK critically revised the project. All authors participated in the preparation of the data. All authors read the final draft of the manuscript and approved it.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data supporting the findings of this study are available on request from the corresponding author.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.