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.
AKR, AKR1B10, cancer, daunorubicin, fibrate.
Department of Chemistry, Youngstown State University, One University Plaza, Youngstown, OH 44555, USA.