are anthracyclines topoisomerase inhibitors?
Another mechanism that has gained ground is the anthracycline activity as Topoisomerase II poisons [28]. After DNA intercalation, anthracycline rings that do not intercalate into the DNA seem to play a role in stabilizing the complex between Topoisomerase II and the DNA that it has nicked. [Molecular determinants of response to topoisomerase II inhibitors]. [Article in French] Lansiaux A(1), Pourquier P. Author information: (1)Centre Oscar Lambret, Université Lille Nord de France. a-Lansiaux@o-lambret.fr Top2 have been used as targets for the development of anticancer drugs. These inhibitors include anthracyclines (doxorubcin, daunorubicin, epirubicin) and epipodophyllotoxins (etoposide), which are widely used in the clinic. These drugs poison Top2 by trapping the enzyme on its DNA cleavage sites, which results in irreversible double-strand breaks that are responsible for cell death. Various other strategies to prevent the cardiotoxicity of anthracyclines are also being employed that include change in administration of the drugs, limiting the overall dosage, encapsulation into liposomes, combination treatment, use of cardioprotectors and synthesis of modified anthracyclines [5]. Doxorubicin and Idarubicin have also been showed to inhibit Topoisomerase I and this is proposed to be an ancillary mechanism of cytotoxic activity of anthracyclines [30]. Anthracyclines, p53 and apoptosis Accumulation of anthracyclines in the nucleus of neoplastic and proliferating cells. Anthracyclines enter the cells through passive diffusion[9]. An elegant mechanism of the selective transport of anthracyclines to the nuclei of neoplastic and proliferating cells has been proposed by Kiyomiya and colleagues[10, 11]. It has been demonstrated with doxorubicin that once it enters the cells, it binds the proteasomes in the cytoplasm for which it has high affinity. Summary. 1  The nuclear enzymes topoisomerase I and II are critical for DNA function and cell survival, and recent studies have identified these enzymes as cellular targets for several clinically active anticancer drugs. Topoisomerase II inhibitors (anthracyclines, epipodophyllotoxins, etc.) are active against several types of tumours. However, treatment with these drugs often results in the development of the multi-drug resistance. Topoisomerase I inhibitors, such as camptothecin and its derivatives, have shown significant activity against a broad range of tumours and, in general, are not substrates for either the multi-drug-resistance P-170 glycoprotein or the multi-drug-resistance-associated protein. Involvement of anthracyclines in inhibiting DNA synthesis by affecting the initiation or the elongation phase, and RNA synthesis by inhibiting RNA polymerase activity has also been documented[25-27]. Another mechanism that has gained ground is the anthracycline activity as Topoisomerase II poisons[28]. Anthracyclines are anticancer compounds that were originally derived from Streptomyces and their anti-tumor activities were established in the 1960s [1]. Anthracyclines are red aromatic polyketides and occur in variety of forms due to the structural differences in the aglycone and the different sugar residues attached [2].
Yes, Anthracyclines and Topoisomerase are inhibitors.