Oleandrin

Oleandrin (PBI-05204) inhibits the Na⁺, K⁺-ATPase activity with an IC₅₀ of 620 nM. IC50 & 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].