Carotenoids Modulate FoxO-Induced Cell Cycle Awrrest in Human Cancer Cell Lines: A Scoping Review

Carotenoids, a class of antioxidants, have shown great potential for cancer management. This scoping review aimed to elucidate the anticancer mechanisms of carotenoids by using a protein interactions and pathways approach. A literature search on five databases (Web of Science, PubMed, Ovid Medline, Ovid Embase and Scopus) was carried out, and studies investigating differential protein expression in cancer cell lines treated with carotenoids published in the last 10 years were included in the analysis. Sixty-three research articles were short-listed, and 17 carotenoids were used in these studies. The most studied carotenoids were fucoxanthin, astaxanthin, and crocin. The key cancer cell lines tested in these studies included breast, gastric, and lung cancers. Analysis of the proteins identified from these studies using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) revealed the upregulation of proteins belonging to the pro-apoptotic and FoxO signaling pathways. In contrast, several proteins in the PI3k/Akt and TNF signaling pathways and cell cycle regulation were downregulated, which can explain the observed anticancer effects. The findings from this scoping review suggest that the cell cycle arrest observed in carotenoid-treated cancer cells may work through activation of the FoxO signaling pathway in these cells, highlighting their role as potential anticancer agents. Nonetheless, the lack of evidence on the pharmacology, pharmacokinetics, and physiology of carotenoids necessitates more robust and well-designed clinical trials. Similarly, further investigations into the therapeutic effects of targeting the PI3K/Akt/FoxO axis to induce cell cycle arrest and its translational potential are required to ensure the successful development of effective treatments.