Pro-death and pro-survival properties of ouabain in U937 lymphoma derived cells

Cuozzo, Francesca; Raciti, Marisa; Bertelli, Laura; Parente, Rosanna; Renzo, Livia Di

doi:10.1186/1756-9966-31-95

Cited by 17 publications

(13 citation statements)

References 38 publications

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“…Several work reported that bufalin or ouabain could cause ROS generation in human colon or lymphoma cancer cells . We here provide further evidence showing the production of ROS in human NSCLC cells upon the CGs treatment.…”

Section: Discussionsupporting

confidence: 73%

Src mediates extracellular signal‐regulated kinase 1/2 activation and autophagic cell death induced by cardiac glycosides in human non‐small cell lung cancer cell lines

Wang

Zhan

et al. 2014

Molecular Carcinogenesis

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Aberrant Na(+) /K(+) -ATPases (NKA) expression is closely related to the incidence and development of cancer, making NKA targeted cancer therapy more intriguing. Cardiac glycosides (CGs) belong to NKA inhibitors and possess potent anti-cancer properties in many cancers. Our previous work demonstrates that CGs family member digoxin or ouabain induces autophagic cell death in human non-small cell lung cancer (NSCLC) cell lines through regulation of both mammalian target of rapamycin and extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. However, what acts as an upstream regulator of ERK1/2 activation during autophagy induction remains obscure. In the present study, the role of Src in the ERK1/2 signaling pathway as well as autophagic cell death induced by either digoxin or ouabain was examined in A549 and H460 cells. Src is significantly activated simultaneously with mitogen-activated protein kinase kinase 1/2 (MEK1/2) and ERK1/2 activation upon the drug treatment. Moreover, Src inhibitor PP2 could block either drug induced MEK1/2 and ERK1/2 phosphorylation, together with autophagic phenotypes in the cells. Knockdown of Src with siRNA causes the similar effect as PP2, both of which markedly alleviate the drugs' cytotoxicity. In addition, increased levels of intracellular reactive oxygen species (ROS) are found to be involved in Src mediated autophagy. Together, this work provides evidences showing that Src mediates MEK1/2 and ERK1/2 pathway as well as ROS generation, and regulates autophagic cell death induced by the cardiac glycosides. These observations may further help understand the molecular mechanisms of autophagy induced by NKA inhibitors in NSCLC cells.

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Section: Discussionsupporting

confidence: 73%

Src mediates extracellular signal‐regulated kinase 1/2 activation and autophagic cell death induced by cardiac glycosides in human non‐small cell lung cancer cell lines

Wang

Zhan

et al. 2014

Molecular Carcinogenesis

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“…Intracellular ROS plays an important role in inducing apoptosis in cancer cells. Previous study showed that Ouabain elevated the cytosolic ROS level in U937 cells [23] and neuroblastoma cell line SH-SY5Y cells [24]. In order to investigate if Peruvoside also induced ROS production in KG1a and K562 leading to apoptosis, we assessed the ROS level in these cells by flow cytometry 24 h after Peruvoside treatment.…”

Section: Resultsmentioning

confidence: 99%

Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death

et al. 2016

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Despite the available chemotherapy and treatment, leukemia remains a difficult disease to cure due to frequent relapses after treatment. Among the heterogeneous leukemic cells, a rare population referred as the leukemic stem cell (LSC), is thought to be responsible for relapses and drug resistance. Cardiac glycosides (CGs) have been used in treating heart failure despite its toxicity. Recently, increasing evidence has demonstrated its new usage as a potential anti-cancer drug. Ouabain, one of the CGs, specifically targeted CD34 + CD38´leukemic stem-like cells, but not the more mature CD34 + CD38 + leukemic cells, making this type of compounds a potential treatment for leukemia. In search of other potential anti-leukemia CGs, we found that Peruvoside, a less studied CG, is more effective than Ouabain and Digitoxin at inducing cell death in primitive myeloid leukemia cells without obvious cytotoxicity on normal blood cells. Similar to Ouabain and Digitoxin, Peruvoside also caused cell cycle arrest at G 2 /M stage. It up-regulates CDKN1A expression and activated the cleavage of Caspase 3, 8 and PARP, resulting in apoptosis. Thus, Peruvoside showed potent anti-leukemia effect, which may serve as a new anti-leukemia agent in the future.

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“…A total of 8−10 discrete foci in each section were examined at 400× to generate an average staining intensity and percentage of stained cells. The final H-score was calculated using the formula: [(1×percentage of weakly stained tumor cells)+(2×percentage of moderately stained tumor cells)+(3×percentage of intensely positive tumor cells)] 34…”

Section: Methodsmentioning

confidence: 99%

<p>Comparison of irisin hormone expression between thyroid cancer tissues and oncocytic variant cells</p>

Uğur¹,

Aydın²,

Kuloğlu³

et al. 2019

CMAR

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Objective: The incidence of thyroid cancer has been continuously increasing. The main objective of this study was to investigate irisin expression in various thyroid pathologies and to compare these expression patterns with irisin expression in healthy thyroid tissues. Methods: The study groups consisted of 20 cases each of control thyroid tissue, Hashimoto’s thyroiditis, thyroid papillary carcinoma, oncocytic papillary carcinoma, follicular thyroid carcinoma, oncocytic follicular thyroid carcinoma, medullary thyroid carcinoma, anaplastic thyroid carcinoma. Irisin expression was evaluated using immunohistochemistry. Irisin levels in thyroid tissue supernatants were measured using ELISA. Results: Patients with HT showed increased irisin expression compared with controls ( p <0.05). In addition, mild immunoreactivity was observed in the thyroid tissues of patients with papillary carcinoma while significantly increased irisin immunoreactivity was observed tissues of patients with oncocytic papillary carcinoma ( p <0.05). There was no difference in irisin immunoreactivity in thyroid tissues between patients with follicular carcinoma and controls. However, irisin immunoreactivity was higher in tissues of patients with oncocytic follicular carcinoma than in tissues of patients with follicular carcinoma ( p <0.05). No irisin immunoreactivity was observed in tissues of patients with medullary carcinoma, a malignant tumor the thyroid; however, irisin expression was significantly increased in tissues of patients with anaplastic carcinoma compared with that in tissues of controls ( p <0.05). Furthermore, in all thyroid tissues with irisin expression, irisin immunoreactivity was observed in follicular cells, indicating that irisin is produced by these cells. Conclusion: Irisin is a novel potential immunohistochemical marker for differentiating oncocytic variants of papillary and FTCs from papillary and follicular thyroid cancers.

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Pro-death and pro-survival properties of ouabain in U937 lymphoma derived cells

Cited by 17 publications

References 38 publications

Src mediates extracellular signal‐regulated kinase 1/2 activation and autophagic cell death induced by cardiac glycosides in human non‐small cell lung cancer cell lines

Src mediates extracellular signal‐regulated kinase 1/2 activation and autophagic cell death induced by cardiac glycosides in human non‐small cell lung cancer cell lines

Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death

<p>Comparison of irisin hormone expression between thyroid cancer tissues and oncocytic variant cells</p>

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