Fibrates Action in Daunorubicin Chemical Reaction
- Pp. 347-357 (11)Ganesaratnam K. Balendiran
Anthracyclines are an important reagent in many chemotherapy regimes for treating a wide range of tumors. One of the primary mechanisms by which anthracycline acts involves DNA damage caused by inhibition of topoisomerase II. Enzymatic detoxification of anthracycline is a critical factor in determining anthracycline resistance. The natural product, daunorubicin, a toxic analogue of anthracycline, is reduced to the less toxic daunorubicinol by the catalytic action of AKR1B10, which is overexpressed in most cases of smoking associated squamous cell carcinoma (SCC) and adenocarcinoma. In addition, AKR1B10 was discovered as an enzyme overexpressed in human liver, cervical, and endometrial cancer cases in samples from uterine cancer patients. The expression of AKR1B10 was also found to be associated with tumor recurrence after surgery and with keratinization of squamous cell carcinoma in cervical cancer. It is estimated to have the potential as a tumor intervention target for colorectal cancer cells (HCT-8) and as a diagnostic marker for non-small-cell lung cancer. This chapter presents the chemical mechanism of action of daunorubicin and a method to improve the effectiveness of daunorubicin by modulating the catalytic activity of AKR1B10.