Rosario Nicoletti

Antagonism against Rhizoctonia solani and fungitoxic metabolite production by some Penicillium isolates

A number of Penicillium isolates were recovered in association to Rhizoctonia solani strains pathogenic on tobacco and from soil on plates pre-colonized by the pathogen itself. Their antagonism toward R. solaniAG-2-1 was evaluated in dual cultures in vitro. Inhibition of growth was evident to some extent in most pairings, while hyphal interactions referable to mycoparasitic relationships were not observed. However, the occurrence of plasmolysis and/or vacuolisation and the induction of monilioid cells were indicative of the release of bioactive compounds. Therefore, production of fungitoxic metabolites was tested by adding concentrated culture filtrates of each Penicillium isolate to the growth medium of R. solani. Complete and lasting inhibition was incited by culture filtrates of some isolates belonging to P. brevicompactum, P. expansum, and P. pinophilum. Three purified compounds, respectively mycophenolic acid, patulin and 3-O-methylfunicone, which were extracted from culture filtrates, were able to inhibit R. solaniin vitro. Their production was also detected in dual cultures of the same Penicilliumstrains with R. solani prepared in sterilized soil and when the Penicilliumstrains were cultured directly on R. solani mycelium harvested from liquid cultures. The possible role of such metabolites in antagonism of the above-mentioned Penicilliumspecies against R. solani is discussed.

Artemisinin reduces human melanoma cell migration by down-regulating αVβ3 integrin and reducing metalloproteinase 2 production

SummaryArtemisinin and its derivatives are well known antimalarial drugs, particularly useful after resistance to traditional antimalarial pharmaceuticals has started to occur in Plasmodium falciparum. In recent years, anticancer activity of artemisinin has been reported both in vitro and in vivo. Artemisinin has inhibitory effects on cancer cell growth and anti-angiogenetic activity. In the present investigation, we analyzed the inhibitory effects of artemisinin on migratory ability of melanoma cell lines (A375P and A375M, low and medium metastatic properties, respectively). We demonstrate that artemisinin induces cell growth arrest in A375M, and affects A375P cells viability with cytotoxic and growth inhibitory effects, while it was not effective in contrasting proliferation of other tumor cell lines (MCF7 and MKN). In addition, artemisinin affected the migratory ability of A375M cells by reducing metalloproteinase 2 (MMP-2) production and down-regulating αvβ3 integrin expression. These findings introduce a potential of artemisinin as a chemotherapeutic agent in melanoma treatment.

Production and fungitoxic activity of Sch 642305, a secondary metabolite of Penicillium canescens

Production of fungitoxic extrolites was evaluated in culture filtrates of several isolates belonging to Penicillium canescens and P. janczewskii that showed some extent of inhibitory activity against the plant pathogenic fungus Rhizoctonia solani. In addition to griseofulvin and dechlorogriseofulvin that are already known in these species, curvulinic acid, previously unreported in Penicillium, was produced by all isolates assayed. Another extrolite recently characterized from a P. verrucosum strain by the name of Sch 642305 was detected in 5 isolates of P. canescens only. The purified compound completely inhibited mycelial growth of isolates of Rhizoctonia solani and other plant pathogenic fungi in␣vitro. The role of this extrolite as a possible biochemical determinant of antagonism toward plant pathogenic fungi, and implications concerning chemotaxonomy are discussed.

3-o-Methylfunicone, a fungitoxic metabolite produced by the fungus Penicillium pinophilum

Abstract The production of 3- o -methylfunicone by Penicillium pinophilum is reported. The compound is ( E )-3-methoxy-2-propenyl-5-(2′-carbomethoxy-4′-6′-dimethoxybenzoyl)-4-pyrone. It completely inhibited growth of Rhizoctonia solani and other species of phytopathogenic fungi cultured on water agar at a concentration of 0.1 mg ml −1 .

Bioactive Compounds Produced by Strains of Penicillium and Talaromyces of Marine Origin

In recent years, the search for novel natural compounds with bioactive properties has received a remarkable boost in view of their possible pharmaceutical exploitation. In this respect the sea is entitled to hold a prominent place, considering the potential of the manifold animals and plants interacting in this ecological context, which becomes even greater when their associated microbes are considered for bioprospecting. This is the case particularly of fungi, which have only recently started to be considered for their fundamental contribution to the biosynthetic potential of other more valued marine organisms. Also in this regard, strains of species which were previously considered typical terrestrial fungi, such as Penicillium and Talaromyces, disclose foreground relevance. This paper offers an overview of data published over the past 25 years concerning the production and biological activities of secondary metabolites of marine strains belonging to these genera, and their relevance as prospective drugs.

Occurence and Bioactivities of Funicone-Related Compounds

Studies on production of secondary metabolites by fungi have received a substantial boost lately, particularly with reference to applications of their biological properties in human medicine. Funicones represent a series of related compounds for which there is accumulating evidence supporting their possible use as pharmaceuticals. This paper provides a review on the current status of knowledge on these fungal extrolites, with special reference to aspects concerning their molecular structures and biological activities.

3-O-methylfunicone, a secondary metabolite produced by Penicillium pinophilum, induces growth arrest and apoptosis in HeLa cells.

Abstract.u2002 3‐O‐Methylfunicone (OMF) is a secondary metabolite produced by the soil fungus Penicillium pinophilum which has cytostatic properties. The aim of this study was to investigate the mechanisms by which such properties are exerted, with special reference to any anti‐proliferative and apoptotic potential, on HeLa cells. OMF treatment caused about 44% inhibition of cell growth after 24 h, and modifications in the tubulin fibre organization. In addition, a significant increase in p21 mRNA expression and a decrease in cyclin D1 and Cdk4 mRNA expression resulted at the same time. Apoptosis induction was demonstrated by the annexin V assay, cytofluorimetric analysis of the DNA content of the sub‐G1 fraction and DNA laddering. Taken together, our data showed that the compound inhibits proliferation of HeLa cells by several mechanisms, such as disruption of tubulin fibres, cell cycle arrest and apoptosis induction. The capacity of the compound to affect the cell cycle and to modulate apoptosis is indicative of a potential for the development of a new agent for cancer chemotherapy.

3‐O‐methylfunicone produced by penicillium pinophilum affects cell motility of breast cancer cells, downregulating αvβ5 integrin and inhibiting metalloproteinase‐9 secretion

Recent evidence assigns integrins and metalloproteinases (MMPs) an important role in regulating tumor cell progression. Here, we demonstrate that 3‐O‐methylfunicone (OMF), a secondary metabolite produced by Penicillium pinophilum, affects cell proliferation and motility of breast cancer MCF‐7 cells, downregulating αvβ5 integrin, and inhibiting MMP‐9 secretion. This effect was absent when the non‐tumoral MCF‐10 cell line was used. Inhibition of cell motility was also associated to modifications in cell shape and in the distribution of tubulin fibers of OMF‐treated MCF‐7 cells. In addition, a possible effect on survivin and hTERT was also investigated. We found that OMF strongly inhibits survivin and hTERT gene expression. The results of this study indicate that OMF‐induced inhibition of cell motility may be mediated through the modulation of αvβ5 integrin and MMP‐9 secretion. In addition, the inhibition of typical markers of tumor progression such as hTERT and survivin in MCF‐7 and their inactivity towards MCF10 provide strong evidence for a potential use of OMF in anticancer therapy.

3-O-methylfunicone, from Penicillium pinophilum, is a selective inhibitor of breast cancer stem cells

Objectives:u2002 Cancer stem cells make up a subpopulation of cells within tumours that drive tumour initiation, growth and recurrence. They are resistant to many current types of cancer treatment, causing failure of such therapeutic approaches, including chemotherapy and radiotherapy. In the study described here, anti‐proliferative effects of 3‐O‐methylfunicone (OMF), a metabolite from Penicillium pinophilum, were investigated on human breast cancer MCF‐7 cells and cancer stem cells selected as mammospheres derived from MCF‐7s.

3- O -methylfunicone, a metabolite of Penicillium pinophilum , inhibits proliferation of human melanoma cells by causing G 2 + M arrest and inducing apoptosis

Objectives:u2002 Melanoma cells take advantage of impaired ability to undergo programmed cell death in response to different external stimuli and chemotherapeutic drugs; this makes prevention of tumour progression very difficult. The aim of this study was to demonstrate whether 3‐O‐methylfunicone (OMF), a metabolite of Penicillium pinophilum, has the ability to arrest cell population growth and to induce apoptosis in A375P (parental) and A375M (metastasis derivatived) melanoma cell lines.