Suchilactone inhibits the growth of acute myeloid leukaemia by inactivating SHP2

Abstract

Context Suchilactone, a lignan compound extracted from Monsonia angustifolia E.Mey. ex A.Rich. (Geraniaceae), has little research on pharmacological activity; whether suchilactone has inhibitory effect on acute myeloid leukaemia (AML) is unclear. Objective To investigate the antitumor effect of suchilactone and its mechanism in AML. Materials and methods The effects of suchilactone on cell growth were detected by CCK-8 and flow cytometry. Network pharmacology was conducted to explore target of suchilactone. Gene expression was detected by western blot and RT-PCR. SHI-1 cells (1 × 106 cell per mouse) were subcutaneously inoculated into the female SCID mice. Suchilactone (15 and 30 mg/kg) was dissolved in PBS with 0.5% carboxymethylcellulose sodium and administered (i.g.) to mice once a day for 19 days, while the control group received PBS with 0.5% carboxymethylcellulose sodium. Tumour tissues were stained with Ki-67 and TUNEL. Results Suchilactone exerted an effective inhibition on the growth of SHI-1 cells with IC50 of 17.01 μM. Then, we found that suchilactone binds to the SHP2 protein and inhibits its activation, and suchilactone interacted with SHP2 to inhibit cell proliferation and promote cell apoptosis via blocking the activation of SHP2. Moreover, Suchilaction inhibited tumour growth of AML xenografts in mice, as the tumour weight decreased from 0.618 g (control) to 0.35 g (15 mg/kg) and 0.258 g (30 mg/kg). Suchilactone inhibited Ki-67 expression and increased TUNEL expression in tumour tissue. Discussion and conclusions Our study is the first to demonstrate suchilactone inhibits AML growth, suggesting that suchilactone is a candidate drug for the treatment of AML.