Lobetyolin induces apoptosis of colon cancer cells by inhibiting glutamine metabolism

The purpose of the present study was to evaluate the anti-cancer property of Lobetyolin on colorectal Cancer and explore its potential mechanism. Lobetyolin was incubated with HCT-116 cells in the absence or presence of ASCT2 Inhibitor Benser or p53 inhibitor Pifithrin-α. The levels of glutamine, glutamic acid, α-ketoglutarate, ATP and GSH were determined to measure the glutamine metabolism. Annexin V-FITC/PI staining and TUNEL assay were applied to estimate the apoptotic condition. The levels of ASCT2 were examined by RT-qPCR, Western blot and immunofluorescence staining. The expressions of cleaved-caspase-3, Caspase-3, cleaved-caspase-7, caspase-7, cleaved-PARP, PARP, p53, p21, Bax and Survivin were detected using Western blot analysis. As a result, the treatment with Lobetyolin effectively induced Apoptosis and glutamine metabolism in HCT-116 cells through ASCT2 signalling. The inhibition of ASCT2 reduced the glutamine-related biomarkers and augmented the apoptotic process. We further found that the effect of Lobetyolin on HCT-116 was related to the expressions of p21 and Bax, and transportation of p53 to nucleus. The inhibition of p53 by Pifithrin-α promoted the inhibitory effect of Lobetyolin on ASCT2-mediated Apoptosis. Lobetyolin also exerted anti-cancer property in nude mice. In conclusion, the present work suggested that Lobetyolin could induce the Apoptosis via the inhibition of ASCT2-mediated glutamine metabolism, which was possibly governed by p53.