Cargando…

Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kang, Yong-Hwi, Lee, Jin-Seok, Lee, Nam-Hun, Kim, Seung-Hyung, Seo, Chang-Seob, Son, Chang-Gue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036817/
https://www.ncbi.nlm.nih.gov/pubmed/33806077
http://dx.doi.org/10.3390/molecules26071856
_version_ 1783676999089258496
author Kang, Yong-Hwi
Lee, Jin-Seok
Lee, Nam-Hun
Kim, Seung-Hyung
Seo, Chang-Seob
Son, Chang-Gue
author_facet Kang, Yong-Hwi
Lee, Jin-Seok
Lee, Nam-Hun
Kim, Seung-Hyung
Seo, Chang-Seob
Son, Chang-Gue
author_sort Kang, Yong-Hwi
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8036817
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80368172021-04-12 Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase Kang, Yong-Hwi Lee, Jin-Seok Lee, Nam-Hun Kim, Seung-Hyung Seo, Chang-Seob Son, Chang-Gue Molecules Article 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. MDPI 2021-03-25 /pmc/articles/PMC8036817/ /pubmed/33806077 http://dx.doi.org/10.3390/molecules26071856 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Kang, Yong-Hwi
Lee, Jin-Seok
Lee, Nam-Hun
Kim, Seung-Hyung
Seo, Chang-Seob
Son, Chang-Gue
Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase
title Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase
title_full Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase
title_fullStr Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase
title_full_unstemmed Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase
title_short Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase
title_sort coptidis rhizoma extract reverses 5-fluorouracil resistance in hct116 human colorectal cancer cells via modulation of thymidylate synthase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036817/
https://www.ncbi.nlm.nih.gov/pubmed/33806077
http://dx.doi.org/10.3390/molecules26071856
work_keys_str_mv AT kangyonghwi coptidisrhizomaextractreverses5fluorouracilresistanceinhct116humancolorectalcancercellsviamodulationofthymidylatesynthase
AT leejinseok coptidisrhizomaextractreverses5fluorouracilresistanceinhct116humancolorectalcancercellsviamodulationofthymidylatesynthase
AT leenamhun coptidisrhizomaextractreverses5fluorouracilresistanceinhct116humancolorectalcancercellsviamodulationofthymidylatesynthase
AT kimseunghyung coptidisrhizomaextractreverses5fluorouracilresistanceinhct116humancolorectalcancercellsviamodulationofthymidylatesynthase
AT seochangseob coptidisrhizomaextractreverses5fluorouracilresistanceinhct116humancolorectalcancercellsviamodulationofthymidylatesynthase
AT sonchanggue coptidisrhizomaextractreverses5fluorouracilresistanceinhct116humancolorectalcancercellsviamodulationofthymidylatesynthase