Inhibition of Topoisomerase IIα by Metal Complexes of Selected Thiosemicarbazones

In vitro inhibition of topoisomerase IIα by reduced glutathione.

In most cells, the major intracellular redox buffer is glutathione (GSH) and its disulfide-oxidized (GSSG) form. The GSH/GSSG system maintains the intracellular redox balance and the essential thiol status of proteins by thiol disulfide exchange. Topoisomerases are thiol proteins and are a target of thiol-reactive substances. In this study, the inhibitory effect of physiological concentration o...

Thiosemicarbazones and Their Transition Metal Complexes

Cyclometalated platinum(II) complexes as topoisomerase IIα poisons.

A platinum(II)-based major groove binder [Pt(II)(C^N)(C≡NR)(2)](+) (HC^N = 2-phenylpyridine (phpy), R = 2-naphthyl) was identified as a potent human topoisomerase IIα poison. It stabilizes the covalent TopoIIα-DNA cleavage complex and induces cancer cell death with potency significantly higher than the widely clinically used TopoIIα poison Vp-16.

Inhibition of Topoisomerase IIα and Induction of Apoptosis in Gastric Cancer Cells by 19-Triisopropyl Andrographolide

Gastric cancer is the most common cancer in Eastern Asia. Increasing chemoresistance and general systemic toxicities have complicated the current chemotherapy leading to an urgent need of more effective agents. The present study reported a potent DNA topoisomerase IIα inhibitory activity of an andrographolide analogue (19-triisopropyl andrographolide, analogue-6) in gastric cancer cells; MKN-45...

Genistein Inhibition of Topoisomerase IIα Expression Participated by Sp1 and Sp3 in HeLa Cell

Genistein (4', 5, 7-trihydroxyisoflavone) is an isoflavone compound obtained from plants that has potential applications in cancer therapy. However, the molecular mechanism of the action of genistein on cancer cell apoptosis is not well known. In this study, we investigated the effect of genistein on topoisomerase II-alpha (Topo IIalpha), an important protein involved in the processes of DNA re...