Anti-tumor Activities of Some Lichen Products and Their Degradation Products

Hirayama, Teruhisa; Fujikawa, Fukujiro; Kasahara, Takashi; Otsuka, Masako; Nishida, Noriko; Mizuno, Den′ichi

doi:10.1248/yakushi1947.100.7_755

Cited by 46 publications

(16 citation statements)

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“…Although there was a difference in potency both substances showed the same type of effect on cell proliferation. The observed in-vitro effects on proliferation and viability of malignant cell-lines can be related to the previously reported anti-tumour activity of protolichesterinic acid against solid type Ehrlich carcinoma in mice (Hirayama et al 1980). We have no obvious explanation of the observed increase in the MTS signal.…”

Section: Donorsupporting

confidence: 64%

Anti-proliferative Effects of Lichen-derived Inhibitors of 5-Lipoxygenase on Malignant Cell-lines and Mitogen-stimulated Lymphocytes

Ögmundsdóttir

Zoëga

Gissurarson

et al. 1998

Journal of Pharmacy and Pharmacology

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Several lichen species have been used traditionally as medicinal plants. It has previously been shown that two low-molecular-weight lichen metabolites, lobaric acid isolated from Stereocaulon alpinum Laur. and protolichesterinic acid isolated from Cetraria islandica L. (Ach.), have in-vitro inhibitory effects on arachidonate 5-lipoxygenase. We have studied the effects of these compounds on cultured cells from man, including three malignant cell-lines (T-47D and ZR-75-1 from breast carcinomas and K-562 from erythro-leukaemia), as well as normal skin fibroblasts and peripheral blood lymphocytes. Both test substances caused a significant reduction in DNA synthesis, as measured by thymidine uptake, in all three malignant cell-lines; the dose inducing 50% of maximum inhibition (ED50) was between 1.1 and 24.6 microg mL(-1) for protolichesterinic acid and between 14.5 and 44.7 microg mL(-1) for lobaric acid. The breast-cancer cell-lines were more sensitive than K-562. The proliferative response of mitogen-stimulated lymphocytes was inhibited with a mean ED50 of 8.4 microg mL(-1) and 24.5 microg mL(-1) for protolichesterinic acid and lobaric acid, respectively. These concentrations are of the same order of magnitude as the IC50 values in the 5-lipoxygenase assay. Significant cell death (assessed by the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-( 4-sulfophenyl)-2H-tetrazolium) assay and trypan blue exclusion) occurred in the three malignant cell-lines at protolichesterinic acid and lobaric acid concentrations above 20 and 30 microg mL(-1), respectively. In K-562 morphological changes consistent with apoptosis were detected. Up to 38% cell death was observed at 20 microg mL(-1) for protolichesterinic acid and 15 microg mL(-1) for lobaric acid in mitogen-stimulated lymphocytes but unstimulated lymphocytes were clearly less sensitive. In contrast, the DNA synthesis, proliferation and survival of normal skin fibroblasts were not affected at doses up to 20 microg mL(-1) for protolichesterinic acid and 30 microg mL(-1) for lobaric acid. We conclude that the anti-proliferative and cytotoxic effects observed might be related to the 5-lipoxygenase inhibitory activity of protolichesterinic acid and lobaric acid. These results open up the opportunity for future studies of these lichen metabolites with regard to their anti-tumour and anti-inflammatory properties.

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Section: Donorsupporting

confidence: 64%

Anti-proliferative Effects of Lichen-derived Inhibitors of 5-Lipoxygenase on Malignant Cell-lines and Mitogen-stimulated Lymphocytes

Ögmundsdóttir

Zoëga

Gissurarson

et al. 1998

Journal of Pharmacy and Pharmacology

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“…Endocrocin and related anthraquinones are noted for their industrial uses as dyes, food additives, components of paper making, and cosmetics (18) as well as for their medicinal uses, including as laxative, anti-inflammatory, and antitumor agents (17,19). Some anthraquinones are also known to be precursors to mycotoxins of global economic and medical importance.…”

mentioning

confidence: 99%

Genome-Based Cluster Deletion Reveals an Endocrocin Biosynthetic Pathway in Aspergillus fumigatus

Lim

Hou

Chen

et al. 2012

Appl Environ Microbiol

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ABSTRACTEndocrocin is a simple anthraquinone frequently identified in extracts of numerous fungi. Several biosynthetic schemes for endocrocin synthesis have been hypothesized, but to date, no dedicated secondary metabolite gene cluster that produces this polyketide as its major metabolite has been identified. Here we describe our biosynthetic and regulatory characterization of the endocrocin gene cluster inAspergillus fumigatus. This is the first report of this anthraquinone in this species. The biosynthetic genes required for endocrocin production are regulated by the global regulator of secondary metabolism, LaeA, and encode an iterative nonreducing polyketide synthase (encA), a physically discrete metallo-β-lactamase type thioesterase (encB), and a monooxygenase (encC). Interestingly, the deletion of a gene immediately adjacent toencC, termedencDand encoding a putative 2-oxoglutarate-Fe(II) type oxidoreductase, resulted in higher levels of endocrocin production than in the wild-type strain, whereas overexpression ofencDeliminated endocrocin accumulation. We found that overexpression of theencAtranscript resulted in higher transcript levels ofencA-Dand higher production of endocrocin. We discuss a model of theenccluster as one evolutionary origin of fungal anthraquinones derived from a nonreducing polyketide synthase and a discrete metallo-β-lactamase-type thioesterase.

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“…Its activity against Ehrlich solid tumor has been confirmed, while other butyrolactone derivatives e.g., nephrosteranic acid had weak activities (Hirayama et al 1980). Lichen glucans do not exhibit antiproliferative activities with impressive IC 50 values on cancer cells as exemplified by the galactomannose substituted a (1 ?…”

Section: Cytotoxic Antimutagenic and Antitumor Activities For Potentmentioning

confidence: 98%

Bioactive lichen metabolites: alpine habitats as an untapped source

2010

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International audienceLichens are fungal and algal/cyanobacterial symbioses resulting in the production of specific metabolites. Some of these are forming an available biomass for phytochemical investigations, including the assessment of biological activities of the isolated compounds. The alpine or polar region are characterised by highly stressful environmental conditions for many organisms, but lichens are among the dominating organisms in these habitats. In the performant mutual protective system, lichen fungi often accumulate high amounts of metabolites with specific physicochemical properties (UV absorbents, hydrophobicity) which help the lichens to survive. Unique secondary metabolites and polysaccharides have been isolated and tested from these organisms. Even though this has been tested until now only with a low number of compounds so far, interesting activities have been recorded. We review here some of the antimicrobial, anti-inflammatory, antiproliferative and antioxidant activities properties described. Solutions with axenic biotechnological cultivation of each symbiotic partner and particularly the mycobiont to obtain the lichen secondary metabolites are challenging to overcome the limitations for the supply of these rare compounds. Additionally, these lichens appear to harbour a diversity of culturable microorganisms from which active compounds have also been isolated recently

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Anti-tumor Activities of Some Lichen Products and Their Degradation Products

Cited by 46 publications

References 0 publications

Anti-proliferative Effects of Lichen-derived Inhibitors of 5-Lipoxygenase on Malignant Cell-lines and Mitogen-stimulated Lymphocytes

Anti-proliferative Effects of Lichen-derived Inhibitors of 5-Lipoxygenase on Malignant Cell-lines and Mitogen-stimulated Lymphocytes

Genome-Based Cluster Deletion Reveals an Endocrocin Biosynthetic Pathway in Aspergillus fumigatus

Bioactive lichen metabolites: alpine habitats as an untapped source

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