Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Low-Molecular-Weight Fucoidan as Complementary Therapy of Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer

Version 1 : Received: 17 June 2021 / Approved: 21 June 2021 / Online: 21 June 2021 (08:55:12 CEST)

A peer-reviewed article of this Preprint also exists.

Huang, C.-W.; Chen, Y.-C.; Yin, T.-C.; Chen, P.-J.; Chang, T.-K.; Su, W.-C.; Ma, C.-J.; Li, C.-C.; Tsai, H.-L.; Wang, J.-Y. Low-Molecular-Weight Fucoidan as Complementary Therapy of Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer. Int. J. Mol. Sci. 2021, 22, 8041. Huang, C.-W.; Chen, Y.-C.; Yin, T.-C.; Chen, P.-J.; Chang, T.-K.; Su, W.-C.; Ma, C.-J.; Li, C.-C.; Tsai, H.-L.; Wang, J.-Y. Low-Molecular-Weight Fucoidan as Complementary Therapy of Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer. Int. J. Mol. Sci. 2021, 22, 8041.

Journal reference: Int. J. Mol. Sci. 2021, 22, 8041
DOI: 10.3390/ijms22158041

Abstract

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF-5-FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the 1) induction of cell cycle arrest in the S phase and 2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both c-mesenchymal–epithelial transition (MET)/ Kirsten Rat Sarcoma virus (KRAS)/ extracellular signal-regulated kinase (ERK) and c-MET/ phosphatidyl-inositol 3-kinases (PI3K)/ protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/ matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required to validate the results of the present study.

Keywords

low-molecular-weight fucoidan; colorectal cancer; HCT116 cell; Caco-2 cell; fluoropyrimidine-based chemotherapy; complementary therapy

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.