Abstract
Colorectal cancer (CRC) is a malignancy of the colon or rectum. It is ranked as the third most common cancer in both men and women worldwide. Early resection permitted by early detection is the best treatment, and chemotherapy is another main treatment, particularly for patients with advanced CRC. A well-known thymidylate synthase (TS) inhibitor, 5-fluorouracil (5-FU), is frequently prescribed to CRC patients; however, drug resistance is a critical limitation of its clinical application. Based on the hypothesis that Coptidis Rhizoma extract (CRE) can abolish this 5-FU resistance, we explored the efficacy and underlying mechanisms of CRE in 5-FU-resistant (HCT116/R) and parental HCT116 (HCT116/WT) cells. Compared to treatment with 5-FU alone, combination treatment with CRE and 5-FU drastically reduced the viability of HCT116/R cells. The cell cycle distribution assay showed significant induction of the G0/G1 phase arrest by co-treatment with CRE and 5-FU. In addition, the combination of CRE and 5-FU notably suppressed the activity of TS, which was overexpressed in HCT116/R cells, as compared to HCT116/WT cells. Our findings support the potential of CRE as an adjuvant agent against 5-FU-resistant colorectal cancers and indicate that the underlying mechanisms might involve inhibition of TS expression.
Highlights
Colorectal cancer (CRC) is the most common malignancy among various cancer types
In the fingerprint analysis of Coptidis Rhizoma extract (CRE), the reference peaks were detected at retention times of 23.50, 28.46, 32.40, and 33.94 min at a UV wavelength of 265 nm
The amount of the four reference compounds were quantified as follows—4.12, 15.03, 33.57, and 146.13 mg/lyophilized g of CRE (Figure 1A,B)
Summary
Colorectal cancer (CRC) is the most common malignancy among various cancer types. In 2020, approximately 1.9 million people were diagnosed with CRC, and 935,000 deaths from CRC occurred worldwide [1]. 5-FU is converted intracellularly to metabolites like fluorouridine triphosphate (FUTP), fluorodeoxyuridine triphosphate (FdUTP), and fluorodeoxyuridine monophosphate (FdUMP) These active metabolites interfere with DNA synthesis by TS [6]. Rhizoma), Fructus Evodiae, Andrographis paniculata, Salvia miltiorrhiza, Hedyotis diffusa, Sophora flavescens, Curcuma longa and Bufo gargarizans, recently attracted a great deal of attention as alternative anticancer therapies to reduce drug resistance [4,18]. Among these medicinal herbs, our group devoted attention to C. Rhizoma against reversing 5-FU resistance in CRC and explored its underlying mechanisms using the HCT116/5-FU cell line
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