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

Alharbi, Yousef; Kapur, Arvinder; Felder, Michael R.; Barroilhet, Lisa; Stein, Timothy J.; Pattnaik, Bikash R.; Patankar, Manish S.

doi:10.1038/s41598-019-47261-x

Cited by 13 publications

(8 citation statements)

References 47 publications

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“…This conclusion was found by Qi et al (2017) who proved PLB induced apoptosis of canine cancer cells via oxidative stress by inhibition of oxidative phosphorylation. Thus, it was concluded that PLB-induced oxidative stress led to the inhibition of NKA in canine cancer cells [ 88 ].…”

Section: Antitumor Activitymentioning

confidence: 99%

Anticancer Effects and Mechanisms of Action of Plumbagin: Review of Research Advances

Yin

Zhang

Chen

et al. 2020

BioMed Research International

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Plumbagin (PLB), a natural naphthoquinone constituent isolated from the roots of the medicinal plant Plumbago zeylanica L., exhibited anticancer activity against a variety of cancer cell lines including breast cancer, hepatoma, leukemia, melanoma, prostate cancer, brain tumor, tongue squamous cell carcinoma, esophageal cancer, oral squamous cell carcinoma, lung cancer, kidney adenocarcinoma, cholangiocarcinoma, gastric cancer, lymphocyte carcinoma, osteosarcoma, and canine cancer. PLB played anticancer activity via many molecular mechanisms, such as targeting apoptosis, autophagy pathway, cell cycle arrest, antiangiogenesis pathway, anti-invasion, and antimetastasis pathway. Among these signaling pathways, the key regulatory genes regulated by PLB were NF-kβ, STAT3, and AKT. PLB also acted as a potent inducer of reactive oxygen species (ROS), suppressor of cellular glutathione, and novel proteasome inhibitor, causing DNA double-strand break by oxidative DNA base damage. This review comprehensively summarizes the anticancer activity and mechanism of PLB.

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Section: Antitumor Activitymentioning

confidence: 99%

Anticancer Effects and Mechanisms of Action of Plumbagin: Review of Research Advances

Yin

Zhang

Chen

et al. 2020

BioMed Research International

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“…12). www.nature.com/scientificreports/ Thus, an inhibition of sodium efflux ATPase would cause an increase in intracellular sodium concentration, which will trigger ROS, DNA damage and, hence, apoptosis [44][45][46] . At the level of cell organelles such as mitochondria, a plausible inhibition of FoF1 ATPase would cause a considerable decrease of ATP and strong changes in depolarization of the mitochondrial membrane 47 .…”

Section: Discussionmentioning

confidence: 99%

Laurinterol from Laurencia johnstonii eliminates Naegleria fowleri triggering PCD by inhibition of ATPases

Arberas-Jiménez

García-Davis

Rizo-Liendo

et al. 2020

Sci Rep

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Primary amoebic encephalitis (PAM) is a lethal disease caused by the opportunistic pathogen, Naegleria fowleri. This amoebic species is able to live freely in warm aquatic habitats and to infect children and young adults when they perform risk activities in these water bodies such as swimming or splashing. Besides the need to increase awareness of PAM which will allow an early diagnosis, the development of fully effective therapeutic agents is needed. Current treatment options are amphotericin B and miltefosine which are not fully effective and also present toxicity issues. In this study, the in vitro activity of various sesquiterpenes isolated from the red alga Laurencia johnstonii were tested against the trophozoite stage of a strain of Naegleria fowleri. Moreover, the induced effects (apoptotic cell death) of the most active compound, laurinterol (1), was evaluated by measuring DNA condensation, damages at the mitochondrial level, cell membrane disruption and production of reactive oxygen species (ROS). The obtained results demonstrated that laurinterol was able to eliminate the amoebae at concentrations of 13.42 ± 2.57 µM and also to induced programmed cell death (PCD) in the treated amoebae. Moreover, since ATP levels were highly affected and laurinterol has been previously reported as an inhibitor of the Na+/K+-ATPase sodium–potassium ion pump, comparison with known inhibitors of ATPases were carried out. Our results points out that laurinterol was able to inhibit ENA ATPase pump at concentrations 100 times lower than furosemide.

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“…In Chapter 4, it has been shown that ROS regulates the activity of SrcK in an NKA signalosome; however, ROS also regulates the NKA pumping activity. Alharbi et al [ 165 ] showed that ROS induced a decrease in the NKA activity, which led to apoptosis of canine cancer cells, and this effect was abrogated by pretreatment with an antioxidant N-acetylcysteine. The mechanism for this regulation of NKA activity lies in the S-glutathionylation of l -Cys residues, which leads to conformational change preventing ATP binding and thus reducing NKA activity [ 166 , 167 ].…”

Section: Regulation Of Na + /K + -Atpase Activitymentioning

confidence: 99%

Na+/K+-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation

et al. 2021

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Maintenance of Na+ and K+ gradients across the cell plasma membrane is an essential process for mammalian cell survival. An enzyme responsible for this process, sodium-potassium ATPase (NKA), has been currently extensively studied as a potential anticancer target, especially in lung cancer and glioblastoma. To date, many NKA inhibitors, mainly of natural origin from the family of cardiac steroids (CSs), have been reported and extensively studied. Interestingly, upon CS binding to NKA at nontoxic doses, the role of NKA as a receptor is activated and intracellular signaling is triggered, upon which cancer cell death occurs, which lies in the expression of different NKA isoforms than in healthy cells. Two major CSs, digoxin and digitoxin, originally used for the treatment of cardiac arrhythmias, are also being tested for another indication—cancer. Such drug repositioning has a big advantage in smoother approval processes. Besides this, novel CS derivatives with improved performance are being developed and evaluated in combination therapy. This article deals with the NKA structure, mechanism of action, activity modulation, and its most important inhibitors, some of which could serve not only as a powerful tool to combat cancer, but also help to decipher the so-far poorly understood NKA regulation.

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

Cited by 13 publications

References 47 publications

Anticancer Effects and Mechanisms of Action of Plumbagin: Review of Research Advances

Anticancer Effects and Mechanisms of Action of Plumbagin: Review of Research Advances

Laurinterol from Laurencia johnstonii eliminates Naegleria fowleri triggering PCD by inhibition of ATPases

Na+/K+-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation

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