Cytotoxic Lanostanoids from <i>Poria cocos</i>

Lai, Kuei-Hung; Lu, Mei‐Chin; Du, Ying-Chi; El-Shazly, Mohamed; Wu, T.-F.; Hsu, Yu Ming; Henz, Astrid; Yang, Juan-Cheng; Backlund, Anders; Chang, Fang‐Rong; Wu, Yang‐Chang

doi:10.1021/acs.jnatprod.6b00575

Cited by 37 publications

(23 citation statements)

References 38 publications

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“…Compounds are placed into a chemical space based on their properties, which can be calculated from simplified molecular input line entry specification (SMILES) structure data, followed by execution of score prediction in ChemGPS-NP. The system provides a bioinformatics tool for plotting and navigating biologically relevant chemical spaces (Larsson et al, 2007; Lai et al, 2016). It can further serve as a tool for discussing the structure-activity relationships as well as to predict possible bioactivities for specific groups of compounds.…”

Section: Resultsmentioning

confidence: 99%

Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP

et al. 2017

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Increasing prevalence of allergic diseases with an inadequate variety of treatment drives forward search for new alternative drugs. Fatty acids, abundant in nature, are regarded as important bioactive compounds and powerful nutrients playing an important role in lipid homeostasis and inflammation. Phytochemical study on Typhonium blumei Nicolson and Sivadasan (Araceae), a folk anti-cancer and anti-inflammatory medicine, yielded four oxygenated fatty acids, 12R-hydroxyoctadec-9Z,13E-dienoic acid methyl ester (1) and 10R-hydroxyoctadec-8E,12Z-dienoic acid methyl ester (2), 9R-hydroxy-10E-octadecenoic acid methyl ester (3), and 12R*-hydroxy-10E-octadecenoic acid methyl ester (4). Isolated compounds were identified by spectroscopic methods along with GC-MS analysis. Isolated fatty acids together with a series of saturated, unsaturated and oxygenated fatty acids were evaluated for their anti-inflammatory and anti-allergic activities in vitro. Unsaturated (including docosahexaenoic and eicosapentaenoic acids) as well as hydroxylated unsaturated fatty acids exerted strong anti-inflammatory activity in superoxide anion generation (IC50 2.14–3.73 μM) and elastase release (IC50 1.26–4.57 μM) assays. On the other hand, in the anti-allergic assays, the unsaturated fatty acids were inactive, while hydroxylated fatty acids showed promising inhibitory activity in A23187- and antigen-induced degranulation assays (e.g., 9S-hydroxy-10E,12Z-octadecadienoic acid, IC50 92.4 and 49.7 μM, respectively). According to our results, the presence of a hydroxy group in the long chain did not influence the potent anti-inflammatory activity of free unsaturated acids. Nevertheless, hydroxylation of fatty acids (or their methyl esters) seems to be a key factor for the anti-allergic activity observed in the current study. Moreover, ChemGPS-NP was explored to predict the structure-activity relationship of fatty acids. The anti-allergic fatty acids formed different cluster distant from clinically used drugs. The bioactivity of T. blumei, which is historically utilized in folk medicine, might be related to the content of fatty acids and their metabolites.

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Section: Resultsmentioning

confidence: 99%

Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP

et al. 2017

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“…P. cocos is an edible and medicinal mushroom of the Polyporaceae family, which is widely used as nutritious food, dietary supplements and traditional medicine in Asia (34,35). Increasing experimental evidence suggests that triterpenes isolated from P. cocos exert direct anticancer effects through a variety of mechanisms, including the inhibition of cell proliferation, induction of apoptosis and suppression of invasive behavior (36)(37)(38)(39)(40). In our previous study, PTE, PA, DPA and PPAC were found to inhibit the growth of pancreatic cancer cells in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

CDC20 associated with cancer metastasis and novel mushroom‑derived CDC20 inhibitors with antimetastatic activity

2019

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Aberrant expression of cell division cycle 20 (CDC20) is associated with malignant progression and poor prognosis in various types of cancer. The development of specific CDC20 inhibitors may be a novel strategy for the treatment of cancer with elevated expression of CDC20. The aim of the current study was to elucidate the role of CDC20 in cancer cell invasiveness and to identify novel natural inhibitors of CDC20. The authors found that CDC20 knockdown inhibited the migration of chemoresistant PANC-1 pancreatic cancer cells and the metastatic MDA-MB-231 breast cancer cell line. By contrast, the overexpression of CDC20 by plasmid transfection promoted the metastasizing capacities of the PANC-1 cells and MCF-7 breast cancer cells. It was also identified that a triterpene mixture extracted from the mushroom Poria cocos (PTE), purified triterpenes dehydropachymic acid, and polyporenic acid C (PPAC) downregulated the expression of CDC20 in PANC-1 cells dose-dependently. Migration was also suppressed by PTE and PPAC in a dose-dependent manner, which was consistent with expectations. Taken together, the present study is the first, to the best of our knowledge, to demonstrate that CDC20 serves an important role in cancer metastasis and that triterpenes from P. cocos inhibit the migration of pancreatic cancer cells associated with CDC20. Further investigations are in progress to investigate the specific mechanism associated with CDC20 and these triterpenes, which may have future potential use as natural agents in the treatment of metastatic cancer.

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“…ChemGPS-NP, a PCA (Principle Component Analysis)-based model applied to natural products, was first developed by the Backlund group in 2007 [ 11 ], and an entire online analysis system that provides the eight principal components (PCs) was further established by the same group in 2009 [ 12 ]. In the last few years, this computational tool has been employed to analyze structure-activity relationships (SAR) [ 13 , 14 ] and to further investigate promising pharmacological targets, guiding natural product drug discovery [ 15 , 16 , 17 ].…”

Section: Resultsmentioning

confidence: 99%

Briaviolides K–N, New Briarane-Type Diterpenoids from Cultured Octocoral Briareum violaceum

Lai

et al. 2018

Marine Drugs

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Four new briarane diterpenoids, briaviolides K–N (1–4), have been obtained from the cultured-type octocoral Briareum violaceum. Using a spectroscopic approach, the structures of briaranes 1–4 were identified. This study employed an in vitro model of lipopolysaccharide (LPS)-induced inflammation in the murine macrophage RAW 264.7 cell line, and found that among the four briaranes, briarane 2 possessed anti-inflammatory activity against inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions in cells. In addition, principal component analysis using the chemical global positioning system (ChemGPS) for natural products (ChemGPS-NP) was employed in order to analyze the structure-activity relationship (SAR), and the results indicated that the ring conformation of the compound has a leading role in suppressing the expressions of pro-inflammatory iNOS and COX-2 proteins in macrophages.

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Cytotoxic Lanostanoids from Poria cocos

Cited by 37 publications

References 38 publications

Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP

Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP

CDC20 associated with cancer metastasis and novel mushroom‑derived CDC20 inhibitors with antimetastatic activity

Briaviolides K–N, New Briarane-Type Diterpenoids from Cultured Octocoral Briareum violaceum

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