Description:
<jats:p>In our preliminary screening study on the protein tyrosine phosphatase 1B (PTP1B) inhibitory and cytotoxic activities, an ethyl acetate soluble fraction of the aerial part of Orthosiphon stamineus Benth. was found to inhibit PTP1B activity. Thus, based on assay-guided isolation of this active fraction, ten compounds (1-10) were purified and evaluated for their inhibitory effects on PTP1B and their growth inhibition on MCF7, tamoxifen-resistant MCF7 (MCF7/TAMR), and MDA-MB-231 human breast cancer cell lines. Among the isolates, compounds 5, 6, 9, and 10 showed potencies against PTP1B with IC<jats:sub>50</jats:sub>values of 9.76, 10.12, 6.88, and 8.92 μM, respectively, followed by compounds 1 and 4 with IC<jats:sub>50</jats:sub>values of 16.92 and 22.25 μM. Kinetic study showed that the active compounds (1, 5, 9, and 10) possessed mixed-competitive inhibition, which was similar to the positive control (ursolic acid, IC<jats:sub>50</jats:sub>value of 3.42 μM, mixed-competitive). The others showed noncompetitive inhibition (4 and 6). In addition, all these active compounds (1, 4-6, and 9-10) displayed growth inhibition on three cancer cell lines, especially the most PTP1B inhibitory flavanones (9 and 10) exhibited comparable inhibitory effects on MCF7, MCF7/TAMR, and MDA-MB-231 cancer cells (IC<jats:sub>50</jats:sub>values of 11.5 and 15.4, 8.9 and 10.5, and 17.6 and 21.3 μM, respectively) with tamoxifen, the positive control used in this assay (IC<jats:sub>50</jats:sub>values of 11.9, 12.1, and 12.7 μM, respectively). The results suggest that these active constituents from O. stamineus might be considered as new natural compounds for the development of anticancer agents via PTP1B inhibition.</jats:p>