Roles of Volume-sensitive Cl− Channel in Cisplatin-induced Apoptosis in Human Epidermoid Cancer Cells

Roles of Volume-sensitive Cl− Channel in Cisplatin-induced Apoptosis in Human Epidermoid Cancer... The anti-cancer drug cisplatin induces apoptosis by damaging DNA. Since a stilbene-derivative blocker of Cl−/HCO 3 − exchangers and Cl− channels, SITS, is known to induce cisplatin resistance in a manner independent of intracellular pH and extracellular HCO 3 − , we investigated the relation between cisplatin-induced apoptosis and Cl− channel activity in human adenocarcinoma KB cells. A stilbene derivative, DIDS, reduced cisplatin-induced caspase-3 activation and cell death, which were detected over 18 h after treatment with cisplatin. DIDS was also found to reduce sensitivity of KB cells to 5-day exposure to cisplatin. Whole-cell patch-clamp recordings showed that KB cells functionally express volume-sensitive outwardly rectifying (VSOR) Cl− channels which are activated by osmotic cell swelling and sensitive to DIDS. Pretreatment of the cells with cisplatin for 12 h augmented the magnitude of VSOR Cl− current. Thus, it is concluded that cisplatin-induced cytotoxicity in KB cells is associated with augmented activity of a DIDS-sensitive VSOR Cl− channel and that blockade of this channel is, at least in part, responsible for cisplatin resistance induced by a stilbene derivative. The Journal of Membrane Biology Springer Journals

Roles of Volume-sensitive Cl− Channel in Cisplatin-induced Apoptosis in Human Epidermoid Cancer Cells

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Copyright © 2005 by Springer Science+Business Media, Inc.
Life Sciences; Human Physiology; Biochemistry, general
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