Investigation of the inhibitory potential of astaxanthin carotenoid on cyclin-dependent kinase 7 (CDK7)

Mutations in molecules that play a key role in the cell cycle lead to uncontrolled cell division, resulting in the transformation of normal cells into tumor cells. Cyclin Dependent Kinases (CDKs) are among the best known and important regulators of the cell cycle. Cyclin Dependent Kinase 7 (CDK7) regulates the cell cycle by phosphorylating and activating the T-loops of CDK1, 2, 4 and 6. In recent years, analyses in various tumor types have shown that CDK7 expression is increased in tumor cells and CDK7 inhibition is effective in inhibiting multiple tumor growths. Among the carotenoids known in nature, astaxanthin is the most potent antioxidant identified so far. Astaxanthin (ATK) is a very potent antioxidant with anti-lipid peroxidation, anti-inflammatory, cardiovascular disease prevention, anti-diabetic and anticancer effects. In this study, the antitumor and cell division retarding effects of ATK carotenoid were investigated through in silico molecular docking of its inhibition potential on CDK7 protein, cell culture studies on MCF10A and MDA-MB-231 human metastatic breast cancer cells, MTT and flow cytometry assays. As a result of the studies, ATK showed high affinity for CDK7 protein in the presence of low binding energy. In addition, ATK showed a cytotoxic effect on MDA-MB-231 tumor cells at a concentration of IC50=9.89 μM after 72 hours of incubation. Cell cycle analysis also revealed that ATK was effective in arresting both cancer and normal cells in G0/G1 phase. The present findings suggest that ATK has cell division retarding activity in addition to its known human health benefits. In conclusion, the present findings provide concrete evidence for the anti-aging potential of ATK and point to the need for more extensive studies in this field.