Ethanolic Fruit Extract of Piper retrofractum Induced Cell Cycle Arrest, Apoptosis, Increased Reactive Oxygen Species Production, and Mitochondrial Dysfunction in Human Cervical Cancer

Cervical cancer remains a significant global health challenge, with high mortality rates and a pressing need for more effective therapeutic options. This study investigates the effects of an ethanolic extract from the fruit of Piper retrofractum (PR) on proliferation and apoptosis in cervical cancer cells. We evaluated the cytotoxicity of the crude ethanolic extract of PR using the sulforhodamine B and colony formation assay. ROS generation, apoptosis, and mitochondrial function were quantified via flow cytometry. The effects on cell migration was assessed using wound healing and Transwell migration assays. The PR extract exhibited a significant inhibitory effect on HeLa cell viability, leading to reduced cancer cell proliferation. The extract induced cell cycle arrest at the G0/G1 phase in a dose‐dependent manner and decreased the proportion of cells in the G2/M phase at concentrations of 100 and 250 µg/mL. Additionally, treatment with the PR extract resulted in a marked increase in ROS production, disruption of mitochondrial function, and inhibition of cell migration. These findings suggest that the PR ethanolic fruit extract exerts substantial antiproliferative, antimigratory, and proapoptotic effects on HeLa cells. Consequently, the PR ethanolic fruit extract holds promise as a potential novel therapeutic agent for the treatment of cervical cancer.