eng Science and Education Publishing Journal of Food and Nutrition Research 2333-1240 2025-12-23 13 12 455 461 10.12691/jfnr-13-12-3 JFNR202513123 article Seon-Hee Kim seonhee@inje.ac.kr, mbdslee@inje.ac.kr 1 Dong Seok Lee seonhee@inje.ac.kr, mbdslee@inje.ac.kr 1 Department of Biomedical Laboratory Science, Inje University, Gimhae, Republic of Korea Cervical cancer remains a significant global health burden, necessitating the development of safer and more effective therapeutic agents. Orostachys japonicus, a traditional medicinal herb, has shown promising anti-cancer activity, but its molecular mechanisms in cervical cancer cells have not been fully elucidated. We investigated the pro-apoptotic effects of the ethyl acetate fraction of O. japonicus (E-OJ) on HeLa cells and compared its activity to known phenolic constituents (kaempferol, quercetin, and gallic acid). Apoptosis was assessed by Annexin V/PI flow cytometry and DAPI staining. Western blot analysis was used to examine NF-百B and MAPK signaling pathways, as well as caspase-3 activation. The role of ERK signaling was further evaluated using the ERK-specific inhibitor U0126. E-OJ treatment induced significant, dose-dependent apoptosis in HeLa cells, accompanied by nuclear fragmentation and chromatin condensation. Compared to individual compounds, E-OJ exhibited greater apoptotic efficacy. Mechanistically, E-OJ suppressed NF-百B signaling by blocking nuclear translocation of the NF-百B p65 subunit. Among the MAPK pathways, only ERK1/2 was activated by E-OJ. Inhibition of ERK1/2 with U0126 attenuated caspase-3 cleavage, indicating that ERK signaling mediates E-OJ-induced apoptosis through a caspase-3-dependent mechanism. These findings suggest that E-OJ induces apoptosis in cervical cancer cells by suppressing NF-百B activation and promoting ERK1/2-mediated caspase-3 activation. The superior efficacy of E-OJ compared to its individual phenolic components highlights its therapeutic potential as a natural anti-cancer agent. https://pubs.sciepub.com/jfnr/13/12/3/jfnr-13-12-3.pdf Orostachys japonicus cervical cancer apoptosis NF-百B ERK1/2