ObjectiveTo explore the effects of the enzymatic glycosylation product modified by enzymatically non-benzoquinone geldanamycin(GA) on the proliferation and apoptosis of breast cancer cells.

MethodsA new non-benzoquinone GA glucoside was prepared using enzymatic glycosylation in vitro.The product was characterized by ESI-MS and nuclear magnetic resonance(NMR) analysis.The anti-cancer activities of the compound were evaluated using malachite green-molybda colour reaction, MTT assay and flow cytometry with PI staining in vitro.The effects of the compound on expression levels of Akt, Bcl-2 and heat shock protein 90(Hsp90) were detected using Western blot.

ResultsThe structure of novel non-benzoquinone GA glucoside was characterized as 17-demethoxy-reblastatin-18-O-β-D-glucopyranoside(1).Compound 1 could significantly inhibit the activity of Hsp90 ATPase, the IC₅₀ value of which was 8.98 μmol/L.Compound 1 could inhibit the proliferation, and induce apoptosis in MCF-7 cells of human breast cancer in a concentration-dependent manner.The results of Western blot showed that, with the increasing of compound 1 concentration, the induced degradation of Akt and bcl-2 protein was more obvious, while the expression of Hsp90 protein was not affected.

ConclusionsThe new Hsp90 inhibitor, compound 1, can inhibit the proliferation, and induce apoptosis of MCF-7 cells, the mechanism of which may be by inhibiting the activity of Hsp90 ATPase, and inducing the degradation of Hsp90 client protein Akt and Bcl-2.