Therapeutic Effects of Cephalotaxus harringtonia Leaf Extract on Hepatocellular Carcinoma via Regulation of the Intrinsic Apoptosis Pathway and Cell Cycle

Apoptosis induction in tumor cells is a fundamental therapeutic approach in cancer treatment, with growing interest in plant-derived compounds that offer potent efficacy and reduced toxicity. <i>Cephalotaxus harringtonia</i>, traditionally used in East Asian medicine, contains several bioactive constituents, including homoharringtonine (HHT) and quercetin 3-β-D-glucoside (Q3G), which are known for their anticancer properties. This study investigated the anticancer effects of <i>C. harringtonia</i> leaf extract (CHLE) and its two major compounds, quercetin 3-β-D-glucoside (Q3G) and HHT, against human liver cancer cell lines (HepG2). CHLE exhibited selective cytotoxicity and apoptosis specifically in HepG2 cells while showing minimal toxicity toward normal kidney cells (HK-2). Mechanistic analyses revealed that CHLE induced apoptosis through a mitochondria-mediated intrinsic pathway, characterized by increased reactive oxygen species production, mitochondrial membrane depolarization, and BAX upregulation. These findings demonstrate that <i>C. harringtonia</i> leaf extract possesses potent, selective anticancer activity and may serve as a promising natural candidate for the prevention and therapeutic management of liver cancer.