Antitumor Activity and Mechanism of Terpenoids in Seaweeds Based on Literature Review and Network Pharmacology

Abstract Seaweeds are a treasure trove of natural secondary metabolites. Terpenoids extracted from seaweeds are shown to possess a variety of antitumor cellular activities. However, due to the complex and diverse structures of terpenoids, their therapeutic targets and complex mechanisms of action have not been clarified. The present study summarises the research on terpenoids from seaweeds in oncological diseases over the last 20 years. Terpenoids show different degrees of inhibitory effects on different types of tumor cells, suggesting that terpenoids in seaweeds may have potential antitumor disease potential. Terpenoids with potential antitumor activity and their mechanism of action are investigated using network pharmacology. A total of 125 terpenoids and 286 targets are obtained. Proto‐oncogene tyrosine‐protein kinase Src(SRC), Signal transducer and activator of transcription 3 (STAT3), Mitogen‐activated protein kinase (MAPK3, MAPK1), Heat shock protein HSP 90‐alpha (HSP90AA1), Phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA), and RAC‐alpha serine/threonine‐protein kinase (AKT1) are defined as core targets. According to GO function and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis, terpenoids may affect the Phoshatidylinositol 3'‐kinase (PI3K)‐Akt signaling pathway, Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, Prostate cancer, MAPK signaling pathway, and Proteoglycans in cancer. In addition, the molecular docking results show that the selected terpenoids are all able to bind strongly to the active protein. Terpenoids may slow down the progression of cancer by controlling apoptosis, proliferation, and protein and enzyme binding.