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Penicillium purpurogenum exerts antitumor effects and ameliorates inflammations in Erlich mice model
bioRxiv - Microbiology Pub Date : 2020-07-02 , DOI: 10.1101/2020.07.02.184291
Amanda Mara Teles , Leticia Prince Pereira Pontes , Sulayne Janayna Araujo Guimarães , Ana Luiza de Araújo Butarelli , Gabriel Xavier Silva , Flavia Raquel Fernandes do Nascimento , Geusa Felipa de Barros Bezerra , Carla Junqueira Moragas Tellis , Rui Miguel Gil da Costa , Marcos Antonio Custódio Neto da Silva , Fernando Almeida-Souza , Ana Paula Silva de Azevedo-Santos , Maria do Desterro Soares Brandao Nascimento

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.

中文翻译:

紫青霉菌在Erlich小鼠模型中发挥抗肿瘤作用并改善炎症

背景生物活性代谢产物的产生有助于真菌抵抗不利的环境条件。一些代谢物通常具有有趣的促进健康的活动。这项研究针对的是从巴西东北部一个受污染的泻湖分离出的青霉青霉的抗肿瘤特性。方法将来自抛光的环境性紫癜体育菌株的提取物进行发酵,过滤,浓缩和冻干,得到乙酸乙酯外提取物(EAE)。使用直接输注质谱法研究了紫青霉菌胞外提取物的代谢产物。实体Ehrlic肿瘤模型用于评估提取物的抗肿瘤活性。将瑞士雌性小鼠分为以下几组(n = 10 /组):用磷酸盐缓冲液处理的阴性对照(CTL-);环磷酰胺(25mg / mL)处理的阳性对照(CTL +);以4、20和100mg / Kg的剂量提取治疗剂;没有肿瘤或治疗的动物(假手术);以及未用中剂量(EAE20)治疗的肿瘤的动物。在15天内每天进行腹膜内所有治疗。之后,对动物进行安乐死,并将肿瘤,淋巴器官和血清用于免疫,组织学和生化参数评估。结果提取物中富含类胡萝卜素。与CLT-相比,所有剂量的提取物均显着减小了肿瘤的大小,并与100%的存活率相关。从组织学上讲,20和100mg / kg的剂量可减少与肿瘤相关的炎症和肿瘤坏死。与CLT-相比,该提取物还减少了淋巴器官的细胞浸润和循环TNF-α水平。提取物未引起体重减轻和肾脏或肝脏毒性变化。结论这些结果表明,来自污染海洋环境的紫癜疟原虫产生萜类途径的杂合天然产物,在体内表现出免疫调节和抗肿瘤特性。因此,真菌发酵是用于生产抗肿瘤剂的生物技术方法。
更新日期:2020-07-03
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