Gedunin

Gedunin is a natural inhibitor of the heat shock protein (Hsp90; Item Nos. 22734 | 22735) co-chaperone p23 that also inhibits Hsp90 expression in human teratocarcinomal NTERA-2 cells in vitro at 5 µg/ml.¹ This tetranortriterpenoid, which is isolated from A. indica, binds to and blocks the chaperone activity of p23 to induce apoptosis in HeLa-PR_B cells in vitro at a concentration of 20 µM.² Gedunin inhibits breast cancer cell proliferation in vitro, with IC₅₀ values of 8.84 and 3.22 µM in MCF-7 and SKBr-3 cells, respectively, and inhibits the growth of PANC-1 pancreatic cancer cells (IC₅₀ = 25 µM) by targeting the sonic hedgehog pathway to induce apoptosis.^3,4 It also exerts anti-inflammatory effects in vivo. In a mouse model of articular inflammation induced by zymosan (Item No. 21175), gedunin (0.05-0.5 mg/kg, i.p.) reduces edema formation and the production of inflammatory cytokines.⁵ Gedunin (0.5 mg/kg) also inhibits the pleural accumulation of eosinophils and activated T lymphocytes in an ovalbumin-sensitized mouse model of allergic inflammation when administered prior to ovalbumin rechallenge.⁶ It also targets the lipopolysaccharide binding site and thus blocks Toll-like receptor 4 (TLR4) signaling in macrophages in vitro at a concentration of 10 µM.⁷

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1. Tharmarajah, L., Samarakoon, S.R., Ediriweera, M.K., et al. In vitro anticancer effect of gedunin on human teratocarcinomal (NTERA-2) cancer stem-like cells. Biomed. Res. Int. 2017, 2413197 (2017).

2. Patwardhan, C.A., Fauq, A., Peterson, L.B., et al. Gedunin inactivates the co-chaperone p23 protein causing cancer cell death by apoptosis. The Journal of Biological Chemisty 288(10), 7313-7325 (2013).

3. Brandt, G.E.L., Schmidt, M.D., Prisinzano, T.E., et al. Gedunin, a novel hsp90 inhibitor: Semisynthesis of derivatives and preliminary structure-activity relationships. J. Med. Chem. 51(20), 6495-6502 (2008).

4. Subramani, R., Gonzalez, E., Nandy, S.B., et al. Gedunin inhibits pancreatic cancer by altering sonic hedgehog signaling pathway. Oncotarget 8(7), 10891-10904 (2017).

5. Conte, F.P., Kerraris, F.K., Costa, T.E.M.M., et al. Effect of gedunin on acute articular inflammation and hypernociception in mice. Molecules 20(2), 2636-2657 (2015).

6. Ferraris, F.K., Moret, K.H., Figueiredo, A.B.C., et al. Gedunin, a natural tetranortriterpenoid, modulates T lymphocyte responses and ameliorates allergic inflammation. Int. Immunopharmacol. 14(1), 82-93 (2012).

7. Borges, P.V., Moret, K.H., Maya-Monteiro, C.M., et al. Gedunin binds to myeloid differentiation protein 2 and impairs lipopolysaccharide-induced toll-like receptor 4 signaling in macrophages. Mol. Pharm. 88(5), 949-961.