Antitumor Potential of <i>Xantolis cambodiana</i> on Human Lung Cancer: Insights Into Reactive Oxygen Species-Mediated Apoptosis and Selective Cytotoxicity

Abstract

Background: Xantolis cambodiana, a Southeast Asian medicinal plant traditionally used to treat inflammation and infections, has not yet been systematically evaluated for its anticancer potential. Objectives: This study investigated the anticancer effects of 4 X. cambodiana extract fractions, including distilled water, methanol, ethyl acetate, and hexane, on human lung cancer A549 cells and explored the associated molecular mechanisms. Methods: Cells were treated with the extracts, and viability and migration were assessed using sulforhodamine B, colony formation, and wound-healing assays. Apoptosis, autophagy, reactive oxygen species (ROS) production, and mitochondrial membrane potential were analyzed by flow cytometry. Results: All fractions showed dose- and time-dependent cytotoxicity at 72 hours, with hexane being the most potent fraction (IC₅₀, 78.18 ± 1.61 μg/mL), followed by ethyl acetate, methanol, and distilled water. Ethyl acetate suppressed colony formation comparably to hexane. At 250 μg/mL, distilled water, methanol, and hexane significantly inhibited cell migration. The extracts induced late apoptosis, most prominently with methanol, ethyl acetate, and hexane (P < 0.05), and triggered autophagy, with the strongest effect observed in the ethyl acetate fraction. These effects were associated with increased ROS production and mitochondrial dysfunction, suggesting ROS-mediated cell death. Conclusions: Xantolis cambodiana extracts demonstrated potent anticancer activity in A549 cells through apoptosis induction and ROS-mediated mitochondrial dysfunction, highlighting their therapeutic potential for lung cancer.