Smilax china root extract as a novel Glucose-6-phosphate dehydrogenase inhibitor for the treatment of hepatocellular carcinoma

A novel therapeutic strategy for cancer treatment is to target altered tumor metabolism. Glucose-6 -phosphate dehydrogenase (G6PD) has been recently discovered to be implicated in apoptosis and angio-genesis, making it an excellent target in cancer treatment. The current study aimed to screen the plant extracts library to find potent hits against G6PD through enzymatic assay. Protein expression was induced by IPTG and purified using Ni-NTA columns after transformation of the pET-24a-HmG6PD plas-mid into E. coli BL21-DE3 strain. An enzymatic assay was established by using purified rG6PD protein, for the screening of G6PD inhibitors. Out of 46 plant extracts screened, the sixteen plant extracts have shown inhibitory activity against the G6PD enzyme. At doses from 1 to 4 mu g/ml, this extract demonstrated concentration-dependent inhibition of G6PD with an IC50 value of I.397 mu g/ml. Moreover, the anticancer activity evaluation against HepG2 cells determined Smilax china as a potent inhibitor of cancer cells (IC50 value of 16.017 mu g/ml). The acute and subacute toxicities were not observed in mice with various con-centrations (50, 100, 200 and 2000 mg/kg). Furthermore, to identify the compounds from Smilax china as G6PD inhibitors, a literature-based phytochemical investigation of Smilax china was conducted, and sixty compounds were docked against the NADP+ and G6P binding sites of G6PD. The results of this study showed that three compounds were Scirpusin A, Smilachinin and Daucosterol with MolDock Score of-156.832,-148.215, and-145.733 respectively, against NADP+ binding site of G6PD. Conclusively, Smilax china root extract could be a safer drug candidate for the treatment of hepatocellular carcinoma.(C) 2022 The Authors. Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

This study screened plant extracts and found that Smilax china root extract has inhibitory effects on G6PD and potential anticancer activity against hepatocellular carcinoma cells. Furthermore, three compounds were identified as potential G6PD inhibitors through phytochemical investigation.