Brusatol

Brusatol (NSC 172924) is a unique inhibitor of the Nrf2 pathway that sensitizes a broad spectrum of cancer cells to Cisplatin and other chemotherapeutic agents. Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism. Brusatol can be developed into an adjuvant chemotherapeutic agent^[1]. Brusatol increases cellular apoptosis^[2]. IC50 & Target:Nrf2^[1] In Vitro: Brusatol (0.05, 0.15, 0.45, 1.35, 4.05 and 12.15 μg/mL) reduces the viability of CT-26 cells in a dose-dependent manner with IC₅₀ value of 0.27±0.01μg/mL. When Brusatol is combined with Cisplatin (CDDP) at a constant concentration ratio of 1:1, cell growth inhibition is markedly enhanced compared with single-agent treatment; the IC₅₀ value of Brusatol and CDDP cotreatment is 0.19±0.02μg/mL^[2].
Brusatol provokes a rapid and transient depletion of Nrf2 protein, through a posttranscriptional mechanism, in mouse Hepa-1c1c7 hepatoma cells. Brusatol sensitizes mammalian cells to chemical toxicity^[3]. In Vivo: Brusatol is able to reach the tumor tissue and inhibit the Nrf2 pathway. Nude mice are injected with A549 cells to induce tumor growth, followed by a single i.p. injection of 2 mg/kg Brusatol. Nrf2 protein levels are significantly decreased at 24 h or 48 h postinjection^[1].
Cisplatin (2 mg/kg) or Brusatol (2 mg/kg) alone does not inhibit tumor growth significantly, whereas in the combination group, tumor size is significantly reduced^[1]. "