Ferroptosis-related biotargets and network mechanisms of fucoidan against colorectal cancer: An integrated bioinformatic and experimental approach

In: International Journal of Biological Macromolecules · 2022 · vol. 222(Pt A) , pp. 1522–1530 · doi:10.1016/j.ijbiomac.2022.09.255 · PMID:36195230 · W4300166994
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This study integrates bioinformatic and experimental approaches to identify ferroptosis-related biotargets and elucidate the network mechanisms through which fucoidan exerts anti-colorectal cancer effects.

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Abstract

Ferroptosis, a type of iron-dependent cell death, has been linked with the occurrence and progression of malignant tumors, including colorectal cancer (CRC). Fucoidan, an algal fucose-rich molecule, has been discovered preclinically to have an anti-CRC signature. Although some underlying mechanisms are reported, many signaling pathways associated with ferroptosis in fucoidan treatment of CRC are still unidentified. In this study, we applied network pharmacology and molecular docking technologies to unmask and identify the medication targets and pharmaceutical mechanisms involved in ferroptosis in fucoidan-treated CRC. 19 ferroptosis-related core targets were identified and enrichment analysis indicated their contribution to pharmacological actions and mechanisms in fucoidan treatment of CRC, including ferroptosis-related signaling pathways. Additional molecular docking verification confirmed that fucoidan docked well with ranked core targets, including transcription factor p65 (RELA), interleukin-1 beta (IL1B), and interleukin-6 (IL6). These in silico findings were validated experimentally in CRC cells following fucoidan treatment. RELA, IL1B, and IL6 expressed positively in human CRC samples. In conclusion, the pharmacological mechanisms of fucoidan in treating CRC may be achieved through multiple biological targets and multiple molecular pathways associated with ferroptosis. Thus, these preclinical findings have laid a theoretical foundation for further research and clinical treatment of CRC using fucoidan.

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