Digoxin Effectively Inhibited Cell Growth and Induced Senescence in Cervical Cancer Cell Line

Tahervand, Atefeh; Parnian, Behnaz; Roudkenar, Mehryar Habibi; Roushandeh, Amaneh Mohammadi

doi:10.5812/gct.14216

Cited by 3 publications

(3 citation statements)

References 21 publications

(21 reference statements)

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“…The NKA complex is sensitive to reactive oxygen radicals (6)(7)(8)(9)(10)(11). We therefore reasoned that the inhibition of NKA activity was a downstream effect of plumbagin, occurring due to the damage of this ion transport complex by the intracellular oxygen radical flux.…”

Section: Nka Inhibitory Activity Is Abrogated By Oxygen Radical Scavementioning

confidence: 99%

“…Therefore, there are initiatives to develop NKA inhibitors as chemotherapeutics for the treatment of cancer. A majority of these studies have focused on digoxin, ouabain and other cardiac glycosides because of their known ability to potently inhibit NKA activity [6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…Oxidative stress also is known to activate protein kinase C (PKC) which in turn phosphorylates NKA [14][15][16][17][18][19]. The phosphorylated form of NKA is internalized from the cell membrane, again resulting in membrane depolarization and cell death (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

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Plumbagin-induced oxidative stress leads to inhibition of Na⁺/K⁺-ATPase (NKA) in canine cancer cells

Alharbi

Kapur²,

Felder

et al. 2019

Preprint

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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 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. KeywordsPlumbagin, Na + /K + -ATPase, oxidative stress, electrophysiology, and canine cancer.

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Section: Nka Inhibitory Activity Is Abrogated By Oxygen Radical Scavementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Plumbagin-induced oxidative stress leads to inhibition of Na⁺/K⁺-ATPase (NKA) in canine cancer cells

Alharbi

Kapur²,

Felder

et al. 2019

Preprint

View full text Add to dashboard Cite

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Plumbagin-induced oxidative stress leads to inhibition of Na+/K+-ATPase (NKA) in canine cancer cells

Alharbi

Kapur

Felder

et al. 2019

Sci Rep

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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.

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Pharmaco-Toxicological Assessment of the Combined Cytotoxic Effects of Digoxin and Betulinic Acid in Melanoma Cells

Rednic

Macaşoi

Pînzaru

et al. 2022

Life

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Betulinic acid, a small molecule from pentacyclic triterpenes class, has been widely studied for its antitumor activity, revealing that it induces the apoptosis of tumor cells in a selective manner. In recent years, digoxin, a cardiac glycoside found particularly in the plant species Digitalis lanata, has drawn interest for its potential antitumor properties. The present study was designed to evaluate the antimelanoma potential of betulinic acid (BA), digoxin (DG), and their association (DG + BA). In vitro assessments were performed 24 h post-treatment on two human melanoma cell lines (SK-Mel-28 and RPMI-7951). In addition, the potential irritant effects of the test samples were evaluated using the chorioallantoic membrane of hen’s eggs. BA and DG exhibit a concentration-dependent cytotoxic activity, with the combination of the two having a more marked effect on the decrease in cell viability (~17% for SK-Mel-28 cells and ~23% for RPMI-7951 cells). Further, morphological changes (rounding of the cells and their separation from the plaque) and alterations in the nucleus and actin fibers (condensation of chromatin and actin fibers, formation of apoptotic bodies) were observed, indicating an apoptotic-like process. Moreover, no irritating effects were observed in ovo. As a result, DG + BA acid may have synergistic potential in the antitumor treatment of melanoma, but future studies are needed in order to clarify the biological mechanisms involved.

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Digoxin Effectively Inhibited Cell Growth and Induced Senescence in Cervical Cancer Cell Line

Cited by 3 publications

References 21 publications

Plumbagin-induced oxidative stress leads to inhibition of Na⁺/K⁺-ATPase (NKA) in canine cancer cells

Plumbagin-induced oxidative stress leads to inhibition of Na⁺/K⁺-ATPase (NKA) in canine cancer cells

Plumbagin-induced oxidative stress leads to inhibition of Na+/K+-ATPase (NKA) in canine cancer cells

Pharmaco-Toxicological Assessment of the Combined Cytotoxic Effects of Digoxin and Betulinic Acid in Melanoma Cells

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