PSEUROTIN A FROM Aspergillus fumigatus Fr. AUMC 8002 EXHIBITS ANTICANCER ACTIVITY AGAINST HEPATOCELLULAR CARCINOMA IN VITRO AND IN VIVO

被引:5
作者
Helal, Gamal A. [1 ]
Ahmed, Fatma A. [2 ]
Askora, Ahmed [1 ]
Saber, Taghred M. [3 ]
Rady, Shimaa M. [1 ,2 ]
机构
[1] Zagazig Univ, Fac Sci, Dept Microbiol & Bot, Zagazig 44519, Egypt
[2] Desert Res Ctr, Med & Aromat Plants Dept, Cairo, Egypt
[3] Zagazig Univ, Fac Vet Med, Forens Med & Toxicol Dept, Zagazig 44519, Egypt
关键词
Aspergillus fumigatus extract; pseurotin A; hepatocellular carcinoma; anticancer; cytotoxic; NITROSODIETHYLAMINE-INDUCED HEPATOCARCINOGENESIS; TUMOR-NECROSIS-FACTOR; N-NITROSODIETHYLAMINE; OXIDATIVE STRESS; ANTIOXIDANT; ALKALOIDS; CHEMOPREVENTION; PREVENTION; APOPTOSIS; MELATONIN;
D O I
10.26873/SVR-610-2019
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
This study investigated the in vitro and in vivo anti-hepatocellular carcinoma activity of pseurotin A isolated from the n-butanol extract of Aspergillus fumigatus Fr. AUMC 8002 (nBE-AF).The in vitro anticancer activity of nBE-AF was measured againsta human hepatocellular carcinoma cell line (HepG2) using a sulforhodamine-B (SRB) assay. The intraperitoneal median lethal dose (LD50) of nBE-AF was determined in rats. Hepatocellular carcinoma was induced in rats by a single intraperitoneal injection of diethylnitrosamine (DEN) (200 mg/kg b.wt.) followed by subcutaneous injections of carbon tetrachloride (CCl4) (3ml/kgb.wt.) weekly for 6 weeks. After administration of these carcinogens, 1/10 and 1/20 LD50 doses of nBE-AF were administered intraperitoneally daily. NBE-AF exhibited significant cytotoxic activity against HepG2 cells. Administration of DEN and CCI4 significantly elevated the serum levels of liver function and tumour markers and significantly downregulated tumour necrosis factor-a gene expression. Moreover, DEN and CCl4 decreased immunohistochemical Bax expression and increased Bcl-2 expression in the liver. Co-treatment with nBE-AF mitigated the DEN+CCl4-induced alterations in a dose-dependent manner. Histopathological evaluation of the liver substantiated the above biochemical results. These results confirmed that nBE-AF, via its major isolated secondary metabolite, pseurotin A, exerted an anti-hepatocarcinogenic effect and could be used as a chemopreventive agent for hepatocellular carcinoma.
引用
收藏
页码:59 / 74
页数:16
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