Doxorubicin hydrochloride (DOX) is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius varcaesius. Doxorubicin binds to nucleic acids, presumably by specific intercalation of the planar anthracycline nucleus with the DNA double helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis. Additionally, doxorubicin inhibits topoisomerase II which results in an increased and stabilized cleavable enzyme-DNA linked complex during DNA replication and subsequently prevents the ligation of the nucleotide strand after double-strand breakage. Doxorubicin also forms oxygen free radicals resulting in cytotoxicity secondary to lipid peroxidation of cell membrane lipids; the formation of oxygen free radicals also contributes to the toxicity of the anthracycline antibiotics, namely the cardiac and cutaneous vascular effects.
Doxorubicin is also a naturally fluorescent anthracycline antibiotic, anticancer drug. It is a substrate of MRP1 which was first cloned from a DOX-resistant lung cancer cell line. Fluorescent property has been exploited for the measurement of drug efflux pump activities as well as resolving the important question of intracellular localization of various multidrug resistance proteins and the role of subcellular organelles (Golgi and lysosome) in the sequestration of drugs and its implication in drug resistant phenotypes.