Oleandrin: A bioactive phytochemical and potential cancer killer via multiple cellular signaling pathways

Kanwal, Nazia; Rasul, Azhar; Hussain, Ghulam; Anwar, Haseeb; Shah, Muhammad Ajmal; Sarfraz, Iqra; Riaz, Ammara; Batool, Rabia; Shahbaz, Muhammad; Hussain, Arif; Selamoğlu, Zeliha

doi:10.1016/j.fct.2020.111570

Cited by 51 publications

(22 citation statements)

References 84 publications

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“…3 Oleandrin is a derivative of the plant Nerium oleander, an ornamental shrub native to Northern Africa, the Eastern Mediterranean Basin, and Southeast Asia. 16,17 Oleandrin is a cardiac glycoside with structures and action similar to those of digoxin. [18][19][20][21] Cardiac glycosides work by inhibiting the enzyme, Na+/K+ ATPase, in the membrane of cardiac myocytes.…”

Section: Oleandrinmentioning

confidence: 99%

Toxicity of herbal medications suggested as treatment for COVID‐19: A narrative review

DiPietro

Mondie

2021

JACEP Open

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Section: Oleandrinmentioning

confidence: 99%

Toxicity of herbal medications suggested as treatment for COVID‐19: A narrative review

DiPietro

Mondie

2021

JACEP Open

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“…Among such potential repurposed drug candidates belong, for example, cardiac glycosides (CGs), currently used in clinical practice for the treatment of heart diseases, such as congestive heart failure or cardiac arrhythmias. Furthermore, CGs also exert very promising anticancer activity both in vitro and in vivo [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ], which is based mainly on the induction of complex signaling cascades in Na + /K + -ATPase (NKA) signalosome and induction of immune response. This fact could be utilized not only for cancer treatment but also in the treatment of a plethora of autoimmune and inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Cardiac Glycosides as Immune System Modulators

2021

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Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various cardiac diseases due to inhibition of Na+/K+-ATPase (NKA) pumping activity and modulating heart muscle contractility. However, recent studies show that the portfolio of diseases potentially treatable with CGs is much broader. Currently, CGs are mostly studied as anticancer agents. Their antiproliferative properties are based on the induction of multiple signaling pathways in an NKA signalosome complex. In addition, they are strongly connected to immunogenic cell death, a complex mechanism of induction of anticancer immune response. Moreover, CGs exert various immunomodulatory effects, the foremost of which are connected with suppressing the activity of T-helper cells or modulating transcription of many immune response genes by inhibiting nuclear factor kappa B. The resulting modulations of cytokine and chemokine levels and changes in immune cell ratios could be potentially useful in treating sundry autoimmune and inflammatory diseases. This review aims to summarize current knowledge in the field of immunomodulatory properties of CGs and emphasize the large area of potential clinical use of these compounds.

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“…In the past few decades, a total of 155 anticancer drugs have been approved for clinical use by the US Food and Drug Administration (FDA), 14% of which are derived from natural products, while 28% are semi-synthetic analogues of natural products, include vinca alkaloids, vincristine, vinblastine, paclitaxel, and their derivative compounds [7][8]. Cardamonin (CAR) is a small molecule chalcone compound extracted from plants belonging to the genus Alpinia of the family Zingiberaceae, such as cardamom [9].…”

Section: Introductionmentioning

confidence: 99%

Cardamonin inhibits the progression of oesophageal cancer by inhibiting the PI3K/AKT signalling pathway

Wang¹,

Liu²,

Hu³

et al. 2021

J. Cancer

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Background: Oesophageal cancer is the most common malignant tumour with a poor prognosis, and the current treatment methods are limited. Therefore, identifying effective treatment methods has become a research hotspot. Cardamonin (CAR) is a natural chalcone compound and has been reported to play an anticancer role in several cancers. However, its function in oesophageal cancer and the possible underlying mechanism are still unclear. The purpose of this study was to demonstrate the anticancer effect of CAR on oesophageal cancer in vivo and in vitro and to explore the underlying mechanism. Materials and Methods: MTT, crystal violet, and colony formation assays were used to detect oesophageal cancer cell proliferation. The effects of CAR on oesophageal cancer cell migration and invasion were detected by wound healing assay and Transwell assay. Hoechst 33258 staining and flow cytometry were used to detect cell apoptosis. Protein expression levels were detected by Western blot. A tumour xenograft model was established to further test the effect of CAR on the growth of oesophageal cancer in vivo. Results: The results showed that CAR inhibited the proliferation, migration, and invasion of oesophageal cancer cells in a concentration-dependent manner and induced apoptosis. Furthermore, the Western blot assay showed that CAR could suppress metastasis by inhibiting epithelial-mesenchymal transition (EMT) as indicated by downregulated expression of the mesenchymal markers N-cadherin and vimentin, the EMT transcription factor Snail, and matrix metalloproteinases (MMPs) and upregulated expression of the epithelial marker E-cadherin. CAR was associated with upregulation of the pro-apoptotic proteins Bax and Bad and downregulation of the anti-apoptotic protein Bcl-2 and triggered the mitochondrial apoptosis pathway, which in turn promoted caspase-3 activation and subsequent cleavage of PARP; however, the mitochondria-related apoptotic effects induced by CAR were blocked by caspase inhibitor Z-VAD-FMK pretreatment, which prevented programmed cell death triggered by CAR. In addition, CAR reduced the phosphorylation level of downstream effector molecules of phosphatidylinositol 3 kinase (PI3K) in a dose-dependent manner, and treatment with the PI3K agonist 740Y-P could partially reverse the anticancer effect of CAR, demonstrating that CAR played an antitumour role by inhibiting the PI3K/AKT signalling pathway in oesophageal cancer cells. Moreover, the EC9706 xenograft model further confirmed that CAR can significantly inhibit tumour growth in vivo. Conclusion:In summary, CAR exhibited a strong anticancer effect on human oesophageal cancer cells and promoted apoptosis by inhibiting the PI3K/AKT signalling pathway, suggesting that CAR can be used as new strategy for oesophageal cancer treatment.

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Oleandrin: A bioactive phytochemical and potential cancer killer via multiple cellular signaling pathways

Cited by 51 publications

References 84 publications

Toxicity of herbal medications suggested as treatment for COVID‐19: A narrative review

Toxicity of herbal medications suggested as treatment for COVID‐19: A narrative review

Cardiac Glycosides as Immune System Modulators

Cardamonin inhibits the progression of oesophageal cancer by inhibiting the PI3K/AKT signalling pathway

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