Pinecone of Pinus koraiensis Inducing Apoptosis in Human Lung Cancer Cells by Activating Caspase-3 and its Chemical Constituents

Pinecones from Pinus koraiensisSiebold & Zucc. (Pinaceae), which have historically been treated as an undesired waste by-product in the processing of seeds, have recently been shown to contain ingredients with potent biological activities, such as polyphenols exhibiting antitumor activity. With this study, we seek to broaden our understanding of antitumor compounds contained in these pinecones beyond just polyphenols. We found that the water extract of P. koraiensis pinecones exhibits significant cytotoxic activity, with IC₅₀ values ranging from 0.62 to 1.73 mg/ml in four human lung cancer cell lines, A549, H1264, H1299, and Calu-6, irrespective of their p53 status. We also demonstrate that pinecone water extract induces apoptosis associated with caspase-3 activation in the same cancer cell lines. Chemical investigation of the pinecone water extract revealed eight main components (1 – 8), and their structures were identified as dehydroabietic acid (1), 15-hydroxy-7-oxodehydroabietic acid (2), 7β,15-dihydroxydehydroabietic acid (3), β-d-glucopyranosyl labda-8(17,13)-diene-(15,16)-lactone-19-oate (4), 7α,15-dihydroxydehydroabietic acid (5), (+)-(1S,2S,4R)-limonene-1,2-diol (6), sobrerol (7), and 4-hydroxybenzoic acid (8). These findings suggest a novel biological application of P. koraiensis pinecones in combatting human lung cancer, and further identify the major compounds that could contribute to this anticancer activity.