Fibrates in the chemical action of daunorubicin.
Anthracyclines are an important reagent in many chemotherapy regimes for treating a wide range of tumors. One of the primary mechanisms of anthracycline action involves DNA damage caused by inhibition of topoisomerase II. Enzymatic detoxification of anthracycline is a major critical factor that determines anthracycline resistance. Natural product, daunorubicin a toxic analogue of anthracycline is reduced to less toxic daunorubicinol by the AKR1B10, enzyme, which is overexpressed in most cases of smoking associate 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. Also, the expression of AKR1B10 was associated with tumor recurrence after surgery and keratinization of squamous cell carcinoma in cervical cancer and estimated to have the potential as a tumor intervention target colorectal cancer cells (HCT-8) and diagnostic marker for non-small-cell lung cancer. This article presents the mechanism of daunorubicin action and a method to improve the effectiveness of daunorubicin by modulating the activity of AKR1B10.
Department of Chemistry, Youngstown State University, One University Plaza, Youngstown, OH 44555, USA. pl_note@yahoo.com
Ganesaratnam K
GK
Balendiran
D000449:Aldehyde Reductase / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D002995:Clofibric Acid / Q000494:pharmacology / Q000627:therapeutic use*; D003630:Daunorubicin / Q000627:therapeutic use*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D013379:Substrate Specificity
D000903:Antibiotics, Antineoplastic; D002995:Clofibric Acid; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D003630:Daunorubicin