A traditional Cameroonian spice, Syzygium guineense curtails leukemia tumor growth through G2-M cell cycle arrest and predicted NLRP3 inflammasome pathway

Abstract

BACKGROUND: S. guineense DC. var. macrocarpum (Engl.) F. White. plant has been a traditional Cameroonian spice used as medicine to treat several health conditions such as liver cirrhosis, vaginal infections, and cancer. OBJECTIVE: This study aims to investigate the anti-cancer effects of Syzygium guineense plant parts on leukemia preclinical models. MATERIAL AND METHODS: Crude extracts and fractions of S. guineense were tested to inhibit the proliferation of human leukemia cells and reduce tumor volume in leukemia xenograft KG1 in immunodeficient mice. Further active fractions were evaluated for the mechanism of action using cell cycle analysis. Inflammasome markers, key targets of chronic inflammation, were screened from phytoconstituents obtained by LC-MS analysis. Of these, putative compounds having potential anticancer efficacy were assessed for kinetic binding with Molecular docking using PyRx-Python Prescription 0.8, and molecular dynamics simulations were performed by GROMACS 22.04. RESULTS: . Computational prediction and GROMACS simulations of these compounds revealed stable binding patterns between the component and target proteins NLRP3 and NEK-7 over 100 ns. CONCLUSION: Our study has provided interesting leads that Cameroonian spice S. guineense fractions/extract exhibited anti-leukemia activity, which could be mediated by inhibiting the innate immune inflammasome pathway. The study emphasizes the importance of S. guineense plant parts that have the potential to be developed for novel targeted therapeutics for leukemia.