Phytochemical profile of bioactive Siraitia grosvenorii root fraction and its potential against nonsmall cell lung cancer in vitro and in vivo

Siraitia grosvenorii (Swingle) C. Jeffrey (SG) is an edible medicinal plant traditionally used to alleviate pulmonary and intestinal diseases in China. Rising demand for SG has led to significant generation of discarded SG roots (SGRs), while previous studies have shown that SGR extract possesses antiproliferative activity against cancer cells. However, its therapeutic potential for nonsmall cell lung cancer (NSCLC) and underlying molecular mechanisms remain uncharacterized. In this study, liquid chromatography ion trap time-of-flight mass spectrometry analysis identified 26 constituents from the active fraction of SGR (SGR2), predominantly categorized as cucurbitane or nor-cucurbitane triterpenoids and their glycosides. SGR2 inhibited the proliferation of A549 cells by inducing apoptosis and cell cycle arrest. In a xenograft tumor model, low-dose SGR2 treatment significantly suppressed tumor growth while exhibiting no observable adverse effects. RNA-seq analysis revealed that SGR2 impacted multiple targets and key pathways relevant to cancer therapy, notably including the JAK/STAT pathway. Western blotting analysis confirmed that SGR2 inhibited the JAK2/STAT3 pathway by reducing phosphorylation expression of JAK2 and STAT3 in both in vitro and in vivo models, and molecular docking studies demonstrated strong binding affinities between active compounds and key target proteins. These findings underscore the remarkable efficacy of SG byproducts and demonstrate their potential applications in NSCLC treatment. The results also contribute to the enhanced productivity and sustainability of SG cultivation.