Antitumor activity of 4-arylcoumarins from endophytic Streptomyces aureofaciens CMUAc130

In a search for antitumor agents, we carried out a screening of 4-arylcoumarins isolated from endophytic Streptomyces aureofaciens CMUAc130, by examining their possible inhibitory effect on the growth of s.c. transplanted Lewis lung carcinoma (LLC) in BDF-1 mice by intraperitoneal (i.p.) administration. The 4-arylcoumarins showed antitumor activity with T/C values of 80.8 and 50.0% at doses of 1 and 10 mg/kg of 5,7-dimethoxy-4-p-methoxylphenylcoumarin treatment, respectively and 81.5 and 44.9% at doses of 1 and 10 mg/kg of 5,7-dimethoxy-4-phenylcoumarin treatment, respectively, compared to adriamycin, which was used a positive control, with T/C value of 55.9% at 2 mg/kg. Furthermore, we investigated the possible effects of these compounds on expression of the bcl-2 and Bax oncoproteins in A427, a human lung cancer cell lines. The cells were cultured in vitro for 24 h in RPMI 1640 with 1.5% (v/v) ethanol, 100 microg/ml 5,7-dimethoxy-4-p-methoxylphenylcoumarin or 5,7-dimethoxy-4-phenylcoumarin. Viability was determined by an MTT assay. Total protein was extracted from cell lysates and the bcl-2 and Bax oncoproteins were identified. Western blotting showed a decrease in bcl-2 and an increase in Bax in A427 cell cultured with 5,7-dimethoxy-4-p-methoxylphenylcoumarin or 5,7-dimethoxy-4-phenylcoumarin. We conclude that 5,7-dimethoxy-4-phenylcoumarin is a more potent inhibitor of cell proliferation than 5,7-dimethoxy-4-p-methoxylphenylcoumarin and has more marked effects on oncoprotein expression.     

Can leaf degrading enzymes provide evidence that endophytic fungi becoming saprobes?

The diversity of endophytic and saprobic fungi from Magnolia liliifera leaves were observed and analyzed to establish relationships. Nine endophytes were morphologically and phylogenetically similar to the saprobes; Colletotrichum gloeosporioides, Colletotrichum sp. 2, Corynespora cassiicola, Fusarium sp. 1, Guignardia mangiferae, Leptosphaeria sp., Phomopsis sp. 2, Phomopsis sp. 6, and Phomopsis sp. 10. The endophytes were found to produce the same degrading enzymes as their saprobic counterparts. The isoform of β-mannanase produced from each of endophyte and saprobe counterparts were similar. Fungal succession and enzyme production patterns during leaf decomposition were correlated. The occurrence of saprobes was found to be related to the enzymes that the fungi produce. The study provides further compelling evidence that endophytes can switch lifestyle to saprobes.     

RETRACTED: Anti-inflammatory Activity of 4-Arylcoumarins from Endophytic Streptomyces aureofaciens CMUAc130 in Murine Macrophage RAW 264.7 Cells

Forty-seven patients with various connective tissue disorders were studied to evaluate the spontaneous release of lymphocyte factors affecting the in vitro migration of guinea pig macrophages. In the assay used the lymphocytes from 8 patients produced an excessive amount of factors inhibiting macrophage migration while the lymphocytes from 12 patients produced an enhancement of migration. There were no differences in the delayed hypersensitivity skin test responses between the 2 groups of patients. The data are consistent with either an abnormality of suppressor lymphocyte function or an altered lymphocyte subpopulation relationship as a factor in this in vitro abnormality.     

Anti-inflammatory activity of 4-arylcoumarins from endophytic Streptomyces aureofaciens CMUAc130 in murine macrophage RAW 264.7 cells

This research was undertaken to test the in vitro anti-inflammatory action of 5,7,4'-trimethoxy-4-phenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin produced by Streptomyces aureofaciens CMUAc130. The effects of the two coumarins were investigated on the formation of NO, PGE2, and TNF-alpha and also on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. The data obtained were consistent with the modulation of iNOS enzyme expression. A similar effect was also observed when LPS-induced PGE2 release and COX-2 expression were tested. The inhibitory effects were shown in concentration-dependent manners. The 5,7,4'-Trimethoxy-4-phenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin also mildly but significantly reduced the formation of TNF-alpha.     

Occurrence and diversity of basidiomycetous endophytes from the oil palm, Elaeis guineensis in Thailand

Fungal endophytes associated with the oil palm, Elaeis guineensis, at an oil palm plantation in Trang Province, Thailand were investigated. Two samplings at the same site yielded 162 and 178 morphotypes. The overall colonization rate was 81 and 87%, respectively, with non-sporulating species being most common. Twenty strains were identified as basidiomycetes using morphological characteristics and confirmed at the molecular level using ribosomal DNA, LSU and ITS sequence data. Species included Fomitopsis cf. meliae, F. cf. ostreiformis, F. cf. pinicola, Perenniporia sp., Pycnoporus sanguineus, Trametes lactinea, and Schizophyllum commune. Leaves supported the greatest number of basidiomycetous taxa (11 strains) with five and four taxa from petioles and rachides, respectively. Twelve taxa produced poroid basidiomes in PDA culture, while the remainder had clamp-connections. Basidiomycetes occurring as saprobes on oil palm were also recorded and compared with those present as endophytes.     

4-arylcoumarin inhibits immediate-type allergy

This study was undertaken to investigate the effect of 4-arylcoumarin (5,7-dimethoxy-4-p-methoxyphenylcoumarin; MPC) on immediate-type allergic reaction and inflammatory cytokine secretion. MPC inhibited compound 48/80-induced systemic reactions in mice. When MPC was given as a pretreatment at concentrations ranging from 0.001 to 1 g/kg, the serum histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. In addition, MPC also inhibited the passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE antibody dose dependently. Furthermore, MPC decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor-α and interleukin-6 secretion in human mast cells. These results indicate that MPC may be beneficial in the treatment of immediate-type allergic reactions.