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

• Published in: International journal of molecular sciences Vol. 22; no. 15; p. 8041
• Main Authors: Huang, Ching-Wen, Chen, Yen-Cheng, Yin, Tzu-Chieh, Chen, Po-Jung, Chang, Tsung-Kun, Su, Wei-Chih, Ma, Cheng-Jen, Li, Ching-Chun, Tsai, Hsiang-Lin, Wang, Jaw-Yuan
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.08.2021; MDPI
• Subjects: Alternative medicine; Apoptosis; Cancer therapies; Cell adhesion & migration; Cell cycle; Chemotherapy; Colorectal cancer; Disease control; Growth factors; Kinases; Metastasis; Mutation; Proteins
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22158041

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-–5FU 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 the c-mesenchymal–epithelial transition (MET)/Kirsten rat sarcoma virus (KRAS)/extracellular signal-regulated kinase (ERK) and the 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 in order to validate the results of the present study.