|Description:||1. Oleandrin, the principal cardiac glycoside component of PBI-05204, can quantitatively account for regulation of BDNF at both the protein and transcriptional levels.|
2. Oleandrin are known to inhibit the Na,K-ATPase pump, resulting in a consequent increase in calcium influx in heart muscle.
3. Oleandrin 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.
4. 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.
5. Oleandrin can mediate the autophagic cell death of human pancreatic tumor cells reducing pAkt and increasing pERK.
6. Oleandrin induces DNA damage responses in cancer cells by suppressing the expression of Rad51.
|Targets:||NF-kB | IL Receptor | EGFR | AP-1 | Sodium Channel | ATPase | Potassium Channel | Akt | ERK | DNA/RNA Synthesis|
|Source:||The herbs of Nerium oleander L.|
|Solvent:||DMSO, Pyridine, Methanol, Ethanol, etc.|
|Storage:||Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C).
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
Need more advice on solubility, usage and handling? Please email to: email@example.com
|After receiving:||The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.|
|1 mg||5 mg||10 mg||20 mg||25 mg|
|1 mM||1.734 mL||8.67 mL||17.34 mL||34.6801 mL||43.3501 mL|
|5 mM||0.3468 mL||1.734 mL||3.468 mL||6.936 mL||8.67 mL|
|10 mM||0.1734 mL||0.867 mL||1.734 mL||3.468 mL||4.335 mL|
|50 mM||0.0347 mL||0.1734 mL||0.3468 mL||0.6936 mL||0.867 mL|
|100 mM||0.0173 mL||0.0867 mL||0.1734 mL||0.3468 mL||0.4335 mL|
Br J Pharmacol. 2014 Jul;171(14):3339-51.
|Short-term exposure to oleandrin enhances responses to IL-8 by increasing cell surface IL-8 receptors.[Pubmed: 24172227]|
|We studied the effects of the plant glycoside Oleandrin on responses to IL-8 in a human monocytic cell line. KEY RESULTS: Pulse exposure to Oleandrin did not induce apoptosis or cytoxicity as observed after non-pulse exposure. Pulse exposure enhanced activation of NF-κB induced by IL-8 but not that induced by TNF-α, IL-1, EGF or LPS. Exposure to other apoptosis-inducing compounds (azadirachtin, resveratrol, thiadiazolidine, or benzofuran) did not enhance activation of NF-κB. Pulse exposure to Oleandrin increased expression of IL-8 receptors and chemotaxis, release of enzymes and activation of NF-κB, NFAT and AP-1 along with increased IL-8-mediated calcineurin activation, and wound healing. Pulse exposure increased numbers of cell surface IL-8 receptors. CONCLUSIONS AND IMPLICATIONS: Short-term (1 h; pulse) exposure to a toxic glycoside Oleandrin, enhanced biological responses to IL-8 in monocytic cells, without cytoxicity. Pulse exposure to Oleandrin could provide a viable therapy for those conditions where leukocyte migration is defective.|
Mol Carcinog. 2014 Apr;53(4):253-63.
|Cellular location and expression of Na+, K+ -ATPase α subunits affect the anti-proliferative activity of oleandrin.[Pubmed: 23073998]|
|The purpose of this study was to investigate whether intracellular distribution of Na(+), K(+) -ATPase α3 subunit, a receptor for cardiac glycosides including Oleandrin, is differentially altered in cancer versus normal cells and whether this altered distribution can be therapeutically targeted to inhibit cancer cell survival. The cellular distribution of Na(+), K(+) -ATPase α3 isoform was investigated in paired normal and cancerous mucosa biopsy samples from patients with lung and colorectal cancers by immunohistochemical staining. The effects of Oleandrin on α3 subunit intracellular distribution, cell death, proliferation, and EKR phosphorylation were examined in differentiated and undifferentiated human colon cancer CaCO-2 cells. Intriguingly, Oleandrin exerted threefold stronger anti-proliferative activity in undifferentiated CaCO-2 cells (IC50, 8.25 nM) than in differentiated CaCO-2 cells (IC50, >25 nM). Oleandrin (10 to 20 nM) caused an autophagic cell death and altered ERK phosphorylation in undifferentiated but not in differentiated CaCO-2 cells. These data demonstrate that the intracellular location of Na(+), K(+) -ATPase α3 isoform is altered in human cancer versus normal cells. These changes in α3 cellular location and abundance may indicate a potential target of opportunity for cancer therapy.|
Pharmacogn Rev. 2013 Jul;7(14):131-9.
|Oleandrin: A cardiac glycosides with potent cytotoxicity.[Pubmed: 24347921]|
|Oleandrin (a toxic cardiac glycoside of N. oleander L.) inhibits the activity of nuclear factor kappa-light-chain-enhancer of activated B chain (NF-κB) in various cultured cell lines (U937, CaOV3, human epithelial cells and T cells) as well as it induces programmed cell death in PC3 cell line culture. The present review focuses the applicability of Oleandrin in cancer treatment and concerned future perspective in the area.|
J Neurosci. 2014 Jan 15;34(3):963-8.
|BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin.[Pubmed: 24431454]|
|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. Together, these findings support further investigation of cardiac glycosides in providing neuroprotection in the context of ischemic stroke.|
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. 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. 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.|
Biochem. Pharmacol.,2004, 66(11):2223-39.
|Oleandrin suppresses activation of nuclear transcription factor-κB and activator protein-1 and potentiates apoptosis induced by ceramide[Reference: WebLink]|
|Ceramide (N-acetyl-D-sphingosine), a second messenger for cell signaling induces transcription factors, like nuclear factor-kappa B (NF-kappa B), and activator protein-1 (AP-1) and is involved in inflammation and apoptosis. Agents that can suppress these transcription factors may be able to block tumorigenesis and inflammation. Oleandrin (trans-3,4',5-trihydroxystilbene), a polyphenolic cardiac glycoside derived from the leaves of Nerium oleander, has been used in the treatment of cardiac abnormalities in Russia and China for years. We investigated the effect of Oleandrin on NF-kappa B and AP-1 activation and apoptosis induced by ceramide. Oleandrin blocked ceramide-induced NF-kappa B activation. Oleandrin-mediated suppression of NF-kappa B was not restricted to human epithelial cells; it was also observed in human lymphoid, insect, and murine macrophage cells. The suppression of NF-kappa B coincided with suppression of AP-1. Ceramide-induced reactive intermediates generation, lipid peroxidation, cytotoxicity, caspase activation, and DNA fragmentation were potentiated by Oleandrin. Oleandrin did not show its activity in primary cells. Oleandrin's anticarcinogenic, anti-inflammatory, and growth-modulatory effects may thus be partially ascribed to the inhibition of activation of NF-kappa B and AP-1 and potentiation of apoptosis.|
Integr Cancer Ther. 2007 Dec;6(4):354-64.
|Autophagic cell death of human pancreatic tumor cells mediated by oleandrin, a lipid-soluble cardiac glycoside.[Pubmed: 18048883]|
|Lipid-soluble cardiac glycosides such as bufalin, Oleandrin, and digitoxin have been suggested as potent agents that might be useful as anticancer agents. Past research with Oleandrin, a principle cardiac glycoside in Nerium oleander L. (Apocynaceae), has been shown to induce cell death through induction of apoptosis. In PANC-1 cells, a human pancreatic cancer cell line, cell death occurs not through apoptosis but rather through autophagy. Oleandrin at low nanomolar concentrations potently inhibited cell proliferation associated with induction of a profound G(2)/M cell cycle arrest. Inhibition of cell cycle was not accompanied by any significant sub G1 accumulation of cells, suggesting a nonapoptotic mechanism. Oleandrin-treated cells exhibited time- and concentration-dependent staining with acridine orange, a lysosomal stain. Subcellular changes within PANC-1 cells included mitochondrial condensation and translocation to a perinuclear position accompanied by vacuoles. Use of a fluorescent Oleandrin analog (BODIPY-Oleandrin) revealed co-localization of the drug within cell mitochondria. Damaged mitochondria were found within autophagosome structures. Formation of autophagosomes was confirmed through electron microscopy and detection of green fluorescent protein-labeled light chain 3 association with autophagosome membranes. Also observed was a drug-mediated inhibition of pAkt formation and up-regulation of pERK. Transfection of Akt into PANC-1 cells or inhibition of pERK activation by MAPK inhibitor abrogated Oleandrin-mediated inhibition of cell growth, suggesting that the reduction of pAkt and increased pERK are important to Oleandrin's ability to inhibit tumor cell proliferation. The data provide insight into the mechanisms and role of a potent, lipid-soluble cardiac glycoside (Oleandrin) in control of human pancreatic cancer proliferation.|
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. 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. 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.|