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BackgroundLung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells.MethodsBioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively.Results and conclusionBioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate–soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with IC50 values ranging from 161.1 μM to 264.6 μM. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.

Previous studies have revealed the antitumor potential of Poria cocos Wolf against a broad spectrum of cancers. However, the biological activity of P. cocos against lung cancer, which is known as the leading cause of cancer mortality worldwide, and its underlying chemical and molecular basis, remain to be investigated. We aimed to evaluate the in vitro cytotoxicity of P. cocos toward human lung adenocarcinoma cells with different p53 statuses, to identify the bioactive constituents of P. cocos, and explicate the molecular mechanisms underlying the cytotoxicity of these constituents in human lung adenocarcinoma cells. An EtOH extract of the sclerotia of P. cocos exhibited cytotoxicity toward four human lung cancer cell lines: A549, H1264, H1299, and Calu-6, regardless of their p53 status. Chemical investigation of the extract resulted in the isolation of two triterpenoids, dehydroeburicoic acid monoacetate (1) and acetyl eburicoic acid (4); a sterol, 9,11-dehydroergosterol peroxide (2); and a diterpenoid, dehydroabietic acid (3). All of the isolated compounds were cytotoxic to the lung adenocarcinoma cell lines, exhibiting IC50 values ranging from 63.6 μM to 171.0 μM at 48 h of treatment. The cytotoxicity of the extract and the isolated compounds were found to be mediated by apoptosis, and accompanied by elevated Bax expression and/or Bcl-2 phosphorylation along with caspase-3 activation. Our data demonstrate that the sclerotium of P. cocos and its four bioactive constituents (1–4) exert cytotoxicity against human lung adenocarcinoma cells, regardless of their p53 status, by inducing apoptosis associated with mitochondrial perturbation, and proposing the potential to employ P. cocos in the treatment of lung cancer.

We identified vulpinic acid as the main constituent that contributes to the cytotoxic activity ofPulveroboletus ravenelii, which has novel biological activity against human cancer cells.

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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 IC 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.

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