Apogossypolone, derivative of gossypol, mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Haseeb ZubairSheikh Mumtaz Hadi

Abstract

Gossypol is a polyphenolic aldehyde that is produced in the cotton plant. Since long it has been reported to possess antiproliferative activity against a variety of cancer cell lines as well as tumor regression in animal models. However, the toxicity of gossypol does not permit it to be an effective antitumor agent. One of the derivatives of gossypol to show promising results is apogossypolone. For example, it has been shown to specifically target tumor growth in hepatocellular carcinoma xenograft in nude mice without causing any damage to normal tissue. Using human peripheral lymphocytes, in this paper we show that both gossypol and its semi-synthetic derivative apogossypolone cause oxidative DNA breakage in these cells through the mobilization of endogenous copper ions. Such cellular DNA breakage is inhibited by copper specific chelator but nor by iron or zinc chelating agents. Similar results are obtained with isolated nuclei indicating that chromatin bound copper is mobilized in this reaction. Further, apogossypolone showed enhanced DNA breakage and increased oxidative stress in whole lymphocytes as compared with gossypol indicating that this is possibly the result of greater permeability of apogossypolone. It is well estab...Continue Reading

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Citations

Jun 19, 2013·Applied Microbiology and Biotechnology·Meiliang ZhouYixiong Tang
Nov 17, 2015·International Journal of Molecular Sciences·Hussain ArifSheikh Mumtaz Hadi
Jan 24, 2014·Oxidative Medicine and Cellular Longevity·Wai-Leng LeeLie-Fen Shyur
May 27, 2017·Current Medicinal Chemistry·Yun ZengDaocheng Wu

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