**3. Anthracycline chemotherapy agents**

Anthracycline antibiotics include DOX, daunorubicin, epirubicin, and idarubicin (**Figure 1**) [9]. DOX and daunorubicin are natural syntheses from *Streptomyces*, although epirubicin and idarubicin are synthetic derivatives from natural products [10]. Anthracyclines have a very high survival rate (~75%) within childhood cancer patients [11]. The drugs have been well recognized as a potential treatment against hematological cancers, including leukemias, lymphomas, solid carcinomas, and sarcomas [10, 12]. All these drugs have been reported to cause cardiotoxicity, classified as an acute and chronic effect [10]. Intracellular anthracycline tends to accumulate in the nucleus at the drug-sensitive cancer cell. However, the drug-resistant cancer cells have been outlined to find the chemotherapic agent at the cytoplasm [10]. Although some mechanism is proposed to explain the molecular structure, including oxidative stress, mitochondrial DNA (mtDNA) damage, etc., the molecular base of anthracycline on noncancerous tissue is still a mystery [12]. Because DOX is the most toxic drug in its class this chapter will evaluate only DOX toxicity, in particular heart damage [10].

**4. Doxorubicin: anticancer antibiotics**

standard cure is in the drug range 10–50 mg/m2

ease, and soft tissue sarcomas [22].

DOX was discovered by Farmitalia Research Laboratories, and they gave it the name Adriamycin after the Adriatic Sea [14]. So, DOX is also known as Adriamycin [15], discovered from *Streptomyces peucetius* (*Streptomyces peucetius* var. *caesius*) in 1967 [16–18]; however, some studies said it was discovered in 1969 [4, 13], and its clinical utilization began in the 1970s [13] after approved in 1974 by the US Food and Drug Administration [19]. DOX is a nonselective class-I anthracyline antibiotic [20]. It has positively charged groups, mannose amine, so that the drug can efficiently bind to a negatively charged molecule, such as nucleic acid. The

Mitochondrial Dysfunction Associated with Doxorubicin http://dx.doi.org/10.5772/intechopen.80284 325

**Figure 1.** The chemical differences between anthracycline antibiotics. Modified from Berthiaume et al. [13].

[18].

DOX has been widely used in the treatment of human and nonhuman tumors, including leukemia [15], lymphomas, soft tissue sarcomas, and solid cancer [21], e.g., breast tumors, osteosarcomas, Kaposi's sarcoma, Hodgkin's and non-Hodkin's lymphomas [14, 22], thyroid and lung carcinomas, stomach, breast, bone, and ovarian cancers [23]. DOX is used for the treatment of solid childhood tumors too, such as non-Hodgkin's lymphomas, Hodgkin's dis-

**Figure 1.** The chemical differences between anthracycline antibiotics. Modified from Berthiaume et al. [13].
