期刊
MARINE DRUGS
卷 16, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/md16110402
关键词
Laminaria japonica; endophyte; Alternaria sp; tricycloalternarene compound; cytotoxicity
资金
- Major Program for The Natural Science Foundation of the Jiangsu Higher Education Institutions of China [17KJA350005]
- Natural Science Foundation of Shandong Province [ZR2015BM016]
- Jiangsu Agriculture Science and Technology Innovation Fund [(18)3007]
The chemical investigation of the culture filtrate of endophyte Alternaria sp. W-1 associated with Laminaria japonica provided a new tricycloalternarene compound, 2H-(2E)-tricycloalternarene 12a (1), together with five known analogs: (2E)-tricycloalternarene 12a (2), tricycloalternarene 3a (3), tricycloalternarene F (4), 15-hydroxyl tricycloalternarene 5b (5), and ACTG-Toxin D (6). In vitro cytotoxicity against the human hepatocellular carcinoma cell line SMMC-7721 and the human gastric carcinoma cell line SGC-7901 was evaluated by the MTT method. Compounds 1, 3, and 4 inhibited the growth of SMMC-7721 cells with IC50 values of 49.7 +/- 1.1, 45.8 +/- 4.6, and 80.3 +/- 3.8 g/mL, respectively, while the IC50 value of the positive control cisplatin was 6.5 +/- 0.5 g/mL. Compounds 3 and 6 also showed moderate anti-proliferation activity against SGC-7901 cells with IC50 values of 53.2 +/- 2.9 and 35.1 +/- 0.8 g/mL, respectively, while the IC50 value of cisplatin was 4.5 +/- 0.6 g/mL. Further studies revealed that the in vitro anticancer activity of compound 3 to SMMC-7721 cells was related to G1 phase cell cycle arrest and cell apoptosis, and the induced apoptosis was involved in both the mitochondrial pathway and the death receptor pathway. This is the first report on the anticancer mechanism of tricycloalternarene compounds.
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