Plumbagin-induced oxidative stress leads to inhibition of Na+/K+-ATPase (NKA) in canine cancer cells
| Autor: | Manish S. Patankar, Bikash R. Pattnaik, Timothy J. Stein, Arvinder Kapur, Yousef Alharbi, Mildred Felder, Lisa Barroilhet |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Radical Science Oxidative phosphorylation Pharmacology Inhibitory postsynaptic potential medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Na+/K+-ATPase 030304 developmental biology Membrane potential 0303 health sciences Multidisciplinary Chemistry Plumbagin respiratory system 3. Good health 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Medicine 030217 neurology & neurosurgery Intracellular Oxidative stress |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) |
| ISSN: | 2045-2322 |
| Popis: | The Na+/K+-ATPase (NKA) complex is the master regulator of membrane potential and a target for anti-cancer therapies. Here, we investigate the effect of drug-induced oxidative stress on NKA activity. The natural product, plumbagin increases oxygen radicals through inhibition of oxidative phosphorylation. As a result, plumbagin treatment results in decreased production of ATP and a rapid increase in intracellular oxygen radicals. We show that plumbagin induces apoptosis in canine cancer cells via oxidative stress. We use this model to test the effect of oxidative stress on NKA activity. Using whole-cell patch-clamp electrophysiology we demonstrate that short-term exposure (4 min) to plumbagin results in 48% decrease in outward current at +50 mV. Even when exogenous ATP was supplied to the cells, plumbagin treatment resulted in 46% inhibition of outward current through NKA at +50 mV. In contrast, when the canine cancer cells were pre-treated with the oxygen radical scavenger, N-acetylcysteine, the NKA inhibitory activity of plumbagin was abrogated. These experiments demonstrate that the oxidative stress-causing agents such as plumbagin and its analogues, are a novel avenue to regulate NKA activity in tumors. |
| Databáze: | OpenAIRE |
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