Secondary metabolites of endophytic fungus Aspergillus puniceus from Eupatorium chinense and its anti-triple negative breast cancer activity and mechanism
WEI Min1, CHEN Lian1, CHEN Jianfeng1, JIN Guilan2, XU Bang2, WANG Qian3, ZOU Kun1, CHENG Fan1, LIU Chengxiong1
(1.Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences,China Three Gorges University, Yichang 443002, Hubei, China; 2.Yichang First People’s Hospital (People’s Hospital Affiliated to China Three Gorges University), Yichang 443002, Hubei, China;3. Yichang Humanwell Pharmaceutical Co., Ltd, Yichang 443002, Hubei, China)
Abstract:An endophytic fungus Aspergillus puniceus was isolated from the root fermentation of Eupatorium chinense. Eight structurally similar xanthones were isolated from the fermentation broth of the strain by normal phase silica gel column chromatography, Sephadex LH-20 gel column chromatography and semi-preparative high performance liquid chromatography. 3′, 4′-hydrogenated austocystins A (1), austocystin M (2), austocystin F (3), austocystin D (4), austocystin B (5), austocystin K (6), austocystin A (7), austocystin H (8) were identified by modern spectroscopic techniques. MTT assay showed that compound 5 had a preferably selective cytotoxicity against triple-negative breast cancer MDA-MB-231 cells with IC50 of 1.28 μmol·L-1. In addition, flow cytometry was used to detect the change of apoptosis rate of MDA-MB-231 cells after treated with compound 5. Compared with the control group, the highest total apoptosis rate was 69.7%. Meanwhile, AO/EB double fluorescence staining also confirmed that compound 5 could induce apoptosis of MDA-MB-231 cells. Mitochondrial membrane potential detection of JC-1 further showed that compound 5 induced apoptosis in MDA-MB-231 cells through mitochondrial pathway.