Penicillium purpurogenumexerts antitumor effects and ameliorates inflammations in Erlich mice model

Abstract

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The bioactive metabolites production contributes to the resistance of fungi towards adverse environmental conditions. Some metabolites often have interesting health-promoting activities. This study addressed the anti-tumoural properties of <jats:italic>Penicillium purpurogenum</jats:italic> isolated from a polluted lagoon in Northeastern Brazil.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The extract obtained from the polished environment strain <jats:italic>P. purpurogenum</jats:italic> was fermented, filtered, concentrated and lyophilized, giving rise to the Ethyl Acetate Extracellular Extract (EAE). The metabolites of the extracellular extract of <jats:italic>P. purpurogenum</jats:italic> were studied using direct infusion mass spectrometry. The solid Ehrlic tumor model was used to evaluate the extract antitumor activity. Female Swiss mice were divided in groups (n=10/group) as follow: Negative control (CTL-) treated with phosphate buffered solution; Positive Control (CTL+) treated with cyclophosphamide (25mg/mL); Extracts treatment at doses 4, 20 and 100mg/Kg; Animals without tumor or treatment (Sham); and animals without tumor treated with intermediate dose (EAE20). All treatments were performed intraperitoneally, daily during 15 days. After, the animals were eutanized and the tumor, lymphoid organs and serum were used for immunological, histological and biochemical parameters evaluation.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The extract was rich in meroterpenoids. All doses of the extract significantly reduced tumor size compared to CLT- and were associated with 100% survival. Histologically, the 20 and 100mg/kg doses reduced tumour-associated inflammation and tumour necrosis. The extract also reduced cellular infiltration of lymphoid organs and circulating TNF-α levels when compared with CLT-. The extract did not induce weight loss and renal or hepatic toxic changes.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>These results indicate that <jats:italic>P. purpurogenum</jats:italic> from a polluted marine environment produce hybrid natural products of the terpenoid pathway that exhibits immunomodulatory and antitumor properties <jats:italic>in vivo</jats:italic>. Thus, fungal fermentation is a biotechnological approach for the production of antitumour agents.</jats:p></jats:sec>