Luffa acutangula (Cucurbitaceae) and Lippia nodiflora (Verbenaceae) have been reputed in the indigenous medicine and claimed to possess a wide array of biological activities including anticancer activity. The present study was designed to assess the in vitro anticancer effect of L. acutangula and L. nodiflora leaf extracts in human lung cancer cell line (NCI-H460). The anticancer activity of both extracts was compared with that of paclitaxel as positive control and the effect was assessed by MTT assay, mitochondrial membrane potential (MMP) alteration, intracellular reactive oxygen species (ROS) measurement and nuclear morphology with the appearance of apoptosis. The leaf extracts exhibits high antiproliferative activity against cell line tested, as determined with MTT assay. The concentrations of growth inhibition at 50% (IC₅₀) ranged from 1 to 50μg/mL after 24h treatment and the IC₅₀ was found to be 20μg/mL and 10μg/mL for L. acutangula and L. nodiflora, respectively. Both extract treated groups exhibits high DCF fluorescence (enhanced ROS levels), significant increase in mitochondrial depolarization when compared to control groups. Nuclear morphology with induction of apoptosis in cells treated with leaf extracts were also observed by microscopic examination using dual staining method of acridine orange-ethidium bromide. The present study suggests the further research such as fractionation and purification of bioactive compounds in order to formulate natural compounds with anticancer activities.