Lactucin inhibits growth and induces apoptosis in gastric cancer cells by targeting MAPK signaling

Introduction: Lactucin, a sesquiterpene lactone isolated from chicory (Cichorium intybus L.), demonstrates broad-spectrum Anticancer activity across multiple malignancies, yet its mechanistic role in gastric Cancer (GC) remains unexplored. This study aimed to elucidate the potential mechanism by which lactucin modulates GC cell proliferation and Apoptosis.

Material and methods: NUGC-3 and MKN-1 cells were used for in vitro studies, and xenograft tumor models were established using BALB/c nude mice for animal studies. To assess cell proliferation, cell cycle distribution, and Apoptosis, CCK-8 assay and flow cytometry analyses were conducted, while cell morphology was examined under an inverted microscope. Levels of proteins associated with cell cycle, Apoptosis, and mitogen-activated protein kinase (MAPK) signaling were determined by Western blotting.

Results: In vitro, lactucin significantly attenuated GC cell proliferation and induced alterations in their morphology. Lactucin induced cell cycle arrest in the G0/G1 phase by reducing protein levels of cyclins (cyclin B1 and cyclin D1) and cyclin-dependent kinases (CDKs), including CDK2 and CDK4. Moreover, lactucin promoted GC cell Apoptosis in a dose-dependent manner by downregulating Bcl-2, upregulating Bax, and increasing cleavage of Caspase-3 and PARP. In vivo, lactucin inhibited tumor growth and decreased Ki67 expression levels in xenograft tumors.

Conclusions: Lactucin inhibited proliferation, induced cell cycle arrest and Apoptosis in GC cells by inactivating the MAPK/p38 pathway.