title: Spectroscopic detection of etoposide binding to chromatin components: the role of histone proteins.
abstract: Chromatin has been introduced as a main target for most anticancer drugs. Etoposide is known as a topoisomerase II inhibitor, but its effect on chromatin components is unknown. This report, for the first time, describes the effect of etoposide on DNA, histones and DNA-histones complex in the structure of nucleosomes employing thermal denaturation, fluorescence, UV absorbance and circular dichroism spectroscopy techniques. The results showed that the binding of etoposide decreased UV absorbance and fluorescence emission intensity, altered secondary structure of chromatin and hypochromicity was occurred in thermal denaturation profiles. The drug exhibited higher affinity to chromatin compared to DNA. Quenching of drug chromophores with tyrosine residues of histones indicated that globular domain of histones is the site of etoposide binding. Moreover, the binding of etoposide to histones altered their secondary structure accompanied with hypochromicity revealing compaction of histones in the presence of the drug. From the results it is concludes that apart from topoisomerase II, chromatin components especially its protein moiety can be introduced as a new site of etoposide binding and histone proteins especially H1 play a fundamental role in this process and anticancer activity of etoposide.
authors: Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors: Elham
authors: E
authors: Chamani
authors: Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. Electronic address: arabbani@ut.ac.ir.
authors: Azra
authors: A
authors: Rabbani-Chadegani
authors: Department of Biotechnology, University of Kashan, Kashan, Iran.
authors: Zohreh
authors: Z
authors: Zahraei
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology*; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000187:drug effects; D013057:Spectrum Analysis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002843:Chromatin; D006657:Histones; D007364:Intercalating Agents; D005047:Etoposide; D004247:DNA
keywords: Anti cancer drugs; Chromatin; Etoposide; Histone proteins