RT Journal Article SR Electronic T1 Penicillium purpurogenum exerts antitumor effects and ameliorates inflammations in Erlich mice model JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.07.02.184291 DO 10.1101/2020.07.02.184291 A1 Amanda Mara Teles A1 Leticia Prince Pereira Pontes A1 Sulayne Janayna Araujo Guimarães A1 Ana Luiza de Araújo Butarelli A1 Gabriel Xavier Silva A1 Flavia Raquel Fernandes do Nascimento A1 Geusa Felipa de Barros Bezerra A1 Carla Junqueira Moragas Tellis A1 Rui Miguel Gil da Costa A1 Marcos Antonio Custódio Neto da Silva A1 Fernando Almeida-Souza A1 Ana Paula Silva de Azevedo-Santos A1 Maria do Desterro Soares Brandao Nascimento YR 2020 UL http://biorxiv.org/content/early/2020/07/02/2020.07.02.184291.abstract AB Background 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 Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil.Methods The extract obtained from the polished environment strain P. purpurogenum was fermented, filtered, concentrated and lyophilized, giving rise to the Ethyl Acetate Extracellular Extract (EAE). The metabolites of the extracellular extract of P. purpurogenum 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.Results 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.Conclusions These results indicate that P. purpurogenum from a polluted marine environment produce hybrid natural products of the terpenoid pathway that exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a biotechnological approach for the production of antitumour agents.ALTalanine aminotransferaseASTaspartate aminotransferaseAUCArea under the curveCTLnegative controlCTL +positive controlEAEethyl acetate extractIFN-γInterferon gammaiNOSinducible nitric oxide synthaseIL-1βinterleukin-1βIL-2interleukin-2IL-4interleukin-4IL-6interleukin-6IL-10interleukin-10IL- 17ainterleukin-17aMCP-1monocyte chemotactic protein-1PImax-1αmacrophage inflammatory protein −1αSEMstandard error of meansTNF-αalpha Tumor Necrosis Factor