| Description: |
Oleandrin has anticarcinogenic, anti-inflammatory, and growth-modulatory effects , which may thus be partially ascribed to the inhibition of activation of NF-κB and AP-1 and potentiation of apoptosis; it has stronger anti-proliferative activity in undifferentiated CaCO-2 cells (IC50, 8.25 nM) , causes an autophagic cell death and altered ERK phosphorylation in undifferentiated.Oleandrin inhibits the Na+, K+-ATPase activity with an IC50 of 620 nM. |
| Targets: |
NF-kB | IL Receptor | EGFR | AP-1 | Sodium Channel | ATPase | Potassium Channel | Akt | ERK | DNA/RNA Synthesis |
| In vitro: |
| Mol Cancer Ther. 2009 Aug;8(8):2319-28. | | Oleandrin-mediated inhibition of human tumor cell proliferation: importance of Na,K-ATPase alpha subunits as drug targets.[Pubmed: 19671733] | Cardiac glycosides such as oleandrin are known to inhibit the Na,K-ATPase pump, resulting in a consequent increase in calcium influx in heart muscle.
METHODS AND RESULTS:
Here, we investigated the effect of oleandrin on the growth of human and mouse cancer cells in relation to Na,K-ATPase subunits. Oleandrin treatment resulted in selective inhibition of human cancer cell growth but not rodent cell proliferation, which corresponded to the relative level of Na,K-ATPase alpha3 subunit protein expression. Human pancreatic cancer cell lines were found to differentially express varying levels of alpha3 protein, but rodent cancer cells lacked discernable expression of this Na,K-ATPase isoform. A correlation was observed between the ratio of alpha3 to alpha1 isoforms and the level of oleandrin uptake during inhibition of cell growth and initiation of cell death; the higher the alpha3 expression relative to alpha1 expression, the more sensitive the cell was to treatment with oleandrin. Inhibition of proliferation of Panc-1 cells by oleandrin was significantly reduced when the relative expression of alpha3 was decreased by knocking down the expression of alpha3 isoform with alpha3 siRNA or increasing expression of the alpha1 isoform through transient transfection of alpha1 cDNA to the cells. Our data suggest that the relative lack of alpha3 (relative to alpha1) in rodent and some human tumor cells may explain their unresponsiveness to cardiac glycosides.
CONCLUSIONS:
In conclusion, the relatively higher expression of alpha3 with the limited expression of alpha1 may help predict which human tumors are likely to be responsive to treatment with potent lipid-soluble cardiac glycosides such as oleandrin. | | Oncotarget, 2016, 7(37):59572-59579. | | Oleandrin induces DNA damage responses in cancer cells by suppressing the expression of Rad51.[Pubmed: 27449097 ] | Oleandrin is a monomeric compound extracted from leaves and seeds of Nerium oleander. It had been reported that oleandrin could effectively inhibit the growth of human cancer cells. However, the specific mechanisms of the oleandrin-induced anti-tumor effects remain largely unclear. Genomic instability is one of the main features of cancer cells, it can be the combined effect of DNA damage and tumour-specific DNA repair defects. DNA damage plays important roles during tumorigenesis. In fact, most of the current chemotherapy agents were designed to kill cancer cells by inducing DNA damage.
METHODS AND RESULTS:
In this study, we found that oleandrin was effective to induce apoptosis in cancer cells, and cause rapid DNA damage response, represented by nuclear RPA (Replication Protein A, a single strand DNA binding protein) and γH2AX(a marker for DNA double strand breaks) foci formation. Interestingly, expression of RAD51, a key protein involved in homologous recombination (HR), was suppressed while XRCC1 was up-regulated in oleandrin treated cancer cells.
CONCLUSIONS:
These results suggested that XRCC1 may play a predominant role in repairing oleandrin-induced DNA damage. Collectively, oleandrin may be a potential anti-tumor agent by suppressing the expression of Rad51. |
|
| In vivo: |
| J Neurosci. 2014 Jan 15;34(3):963-8. | | BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin.[Pubmed: 24431454] | We have previously shown that the botanical drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, provides neuroprotection in both in vitro and in vivo brain slice-based models for focal ischemia (Dunn et al., 2011). Intriguingly, plasma levels of the neurotrophin BDNF were increased in patients treated with PBI-05204 in a phase I clinical trial (Bidyasar et al., 2009).
METHODS AND RESULTS:
We thus tested the hypothesis that neuroprotection provided by PBI-05204 to rat brain slices damaged by oxygen-glucose deprivation (OGD) is mediated by BDNF. We found, in fact, that exogenous BDNF protein itself is sufficient to protect brain slices against OGD, whereas downstream activation of TrkB receptors for BDNF is necessary for neuroprotection provided by PBI-05204, using three independent methods. Finally, we provide evidence that oleandrin, the principal cardiac glycoside component of PBI-05204, can quantitatively account for regulation of BDNF at both the protein and transcriptional levels.
CONCLUSIONS:
Together, these findings support further investigation of cardiac glycosides in providing neuroprotection in the context of ischemic stroke. |
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