Expression levels of Human Aldo-Keto Reductase ( AKR1C) Enzymes in breast cancer cells under treatment of natural compounds

Human aldo–keto reductases AKR1C1- AKR1C4 are involved in the biosynthesis and inactivation of steroid hormones and prostaglandins, lipid peroxidation and in xenobiotics metabolism. Altered expression of AKR1Cs has been observed in a variety of primary human cancers. Development of anticancer drug resistance has also been associated with altered expression of the AKR1C isoforms. The transcription factors NF-Y, Sp1 regulate the transcription of AKR1C1 gene. The phorbol ester response element or AP-1 site is located in the AKR1C1 gene promoter. AKRC1–3 are regulated via Nrf2, a transcription factor that activates these genes trough binding specifically to the ARE in response to oxidative stress and treatment with dietary phytochemicals. Several of phytochemicals such as flavonoid luteolin is known to be potent Nrf2 inhibitors. And on the other hand several of AKR1C enzymes have been shown to be induced by chemopreventive agents. Here we have tested AKR1C enzymes alterations at both the mRNA and the protein activity in MCF7 breast cancer cells that were treated with various concentrations of a group of alkaloids for 48h. An inhibition potency is seen from almost no change to promisingly strong suppression in members of this group of phytochemicals, more or less depending on various structures.