Oleandrin

Names

[ CAS No. ]:
465-16-7

[ Name ]:
Oleandrin

[Synonym ]:
(3β,5β,16β)-16-(acetyloxy)-3-[(2,6-dideoxy-3-O-methyl-α-L-arabino-hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide
Corrigen
OLEANDRIN
Neriolin
(3β,5β,16β)-16-Acetoxy-3-[(2,6-dideoxy-3-O-methyl-α-L-arabino-hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide
Cholesteryl-methyl-ether
Card-20(22)-enolide, 16-(acetyloxy)-3-((2,6-dideoxy-3-O-methyl-α-L-arabino-hexopyranosyl)oxy)-14-hydroxy-, (3β,5β,16β)-
Cholesterin-methylether
Card-20(22)-enolide, 16-(acetyloxy)-3-[(2,6-dideoxy-3-O-methyl-α-L-arabino-hexopyranosyl)oxy]-14-hydroxy-, (3β,5β,16β)-
(3b,5b,16b)-16-(Acetyloxy)-3-[(2,6-dideoxy-3-O-methyl-a-L-arabino-hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide
Folinerin
Cholesterin-monomethylether
EINECS 207-361-5

Biological Activity

[Description]:

Oleandrin inhibits the Na+, K+-ATPase activity with an IC50 of 620 nM.

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Na+/K+ ATPase

Research Areas >> Cancer

[Target]

IC50: 620 nM (Na+, K+-ATPase)[1].

[In Vitro]

Study of Na,K-ATPase inhibition shows an IC50 (nM) of 620 for Oleandrin. The inhibition of Na,K-ATPase by Oleandrin confirms that it likely exert its toxic effect through inhibition of sodium pump activity[1]. When treated with a series of concentrations of Oleandrin (0.2-25 nM), the undifferentiated CaCO-2 cells are sensitive as evidenced by an IC50 of 8.25 nM. In contrast, a maximum growth inhibition of only 20% is reached in differentiated CaCO-2 cells even though they are treated with Oleandrin concentrations as high as 25 nM[2].

[In Vivo]

The effect of Oleandrin is investigated on glioma growth in vivo. To this aim, SCID or C57BL/6 mice are transplanted, respectively, with human U87MG (5×104), U251, GBM19 (5×105), or murine (syngeneic) GL261 (7.5×104) cells into the right striatum and, after 10 d, treated daily with intraperitoneal Oleandrin for an additional 7 d. Oleandrin significantly reduces tumor sizes in human and murine glioma cell models in vivo in a dose-dependent way. High concentrations of Oleandrin (3 mg/kg) are fatal in both models, as expected from the known lethal dose for rodents. Doses of Oleandrin below the lethal dose (0.3 mg/kg) significantly increase the survival time from 32.6±1.4 d to 53.8±9.6 d in mice injected with U87MG cells (n=5-11; p<0.01, log-rank test) and from 23.37±1.2 d to 34.38±3.3 d (n=5-11; p<0.01, log rank test) in mice injected with GL261 cells[3].

[Cell Assay]

Undifferentiated wild-type and well-differentiated CaCO-2 cells are treated with a range of concentrations of Oleandrin (0.2-25 nM). After 48 h, cells are labeled with BrdU and relative cell proliferation is determined with a BrdU Cell Proliferation Kit[2].

[Animal admin]

Mice[3] After tumor cell injection, SCID or C57BL/6 mice are monitored daily. The end point is determined by lack of physical activity or death. The mean survival time is calculated using the Kaplan-Meier method and statistical analysis is performed using a log-rank test. For cotreatment with Temozolomide (TMZ), 10 d after tumor injection, mice are treated with Oleandrin (0.03, 0.3, or 3 mg/kg/daily, i.p.), TMZ (50 mg/kg, i.p., every 2 d for a total of 4 times with a stop of 2 weeks) or both. The dosing scheme is chosen starting from these data to be reasonably sure that a constant concentration of drug is maintained along the experiment. Animals used in Kaplan-Meier survival studies receive up to four TMZ cycles.

[References]

[1]. Jortani SA, et al. Inhibition of Na,K-ATPase by oleandrin and oleandrigenin, and their detection by digoxin immunoassays. Clin Chem. 1996 Oct;42(10):1654-8.

[2]. Yang P, et al. Cellular location and expression of Na⁺, K⁺-ATPase α subunits affect the anti-proliferative activity of oleandrin. Mol Carcinog. 2014 Apr;53(4):253-63.

[3]. Garofalo S, et al. The Glycoside Oleandrin Reduces Glioma Growth with Direct and Indirect Effects on Tumor Cells. J Neurosci. 2017 Apr 5;37(14):3926-3939.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.26

[ Boiling Point ]:
693.7±55.0 °C at 760 mmHg

[ Melting Point ]:
250ºC

[ Molecular Formula ]:
C₃₂H₄₈O₉

[ Molecular Weight ]:
576.718

[ Flash Point ]:
217.2±25.0 °C

[ Exact Mass ]:
576.329834

[ PSA ]:
120.75000

[ LogP ]:
2.30

[ Vapour Pressure ]:
0.0±4.9 mmHg at 25°C

[ Index of Refraction ]:
1.567

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H300 + H330-H373

[ Precautionary Statements ]:
P260-P264-P284-P301 + P310-P310

[ Hazard Codes ]:
T

[ Risk Phrases ]:
23/24/25

[ Safety Phrases ]:
22-36/37/39-45

[ RIDADR ]:
UN 2811

[ RTECS ]:
FH4585000

Articles

Rapid detection of convallatoxin using five digoxin immunoassays.

Clin. Toxicol. (Phila.) 52(7) , 659-63, (2014)

Cardiac glycosides of plant origin are implicated in toxic ingestions that may result in hospitalization and are potentially lethal. The utility of commonly available digoxin serum assays for detectin...

PBI-05204, a supercritical CO₂ extract of Nerium oleander, inhibits growth of human pancreatic cancer via targeting the PI3K/mTOR pathway.

Invest. New Drugs 33(2) , 271-9, (2015)

Introduction Oleandrin, a cardiac glycoside, exerts strong anti-proliferative activity against various human malignancies in in vitro cells. Here, we report the antitumor efficacy of PBI-05204, a supe...

BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin.

J. Neurosci. 34(3) , 963-8, (2014)

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...