The Cytotoxic Constituents of Betula platyphylla and their Effects on Human Lung A549 Cancer Cells

ABSTRACT

During the screening for cytotoxic compounds from plants grown in Korea, Betula platyphylla (BP) showed potent activity against the adenocarcinomic human alveolar basal epithelial A549 cell line. To identify the cytotoxic components from BP, the CH₂Cl₂ fraction with the most significant cytotoxic effect was applied to the column chromatographies. Seven compounds were isolated lupeol (1), betulinic acid (2), (−)-rhododendrol (3), platyphyllenone (4), platyphyllone (5), (−)-centrolobol (6), and oleanolic acid (7). Among them, three diarylheptanoids (4 – 6) exhibited cytotoxicity toward A549 cells. Especially, 50 µM of 4 reduced A549 cell viability to 18.93 ± 0.82% compared to control (100.00 ± 21.48%). Lactate dehydrogenase (LDH) leakage and intracellular reactive oxygen species (ROS) production were also induced by 50 µM 4. This is the first report on the cytotoxic effect of BP-derived diarylheptanoids 4–6 against A549 cells. The compound 4 may be useful for the development of early hit compounds for non-small cell lung carcinoma, but the consideration about selectivity of 4 is required since 4 also showed the cytotoxicity in the human normal lung epithelial BEAS-2B cell line.