期刊
MARINE DRUGS
卷 13, 期 8, 页码 4733-4753出版社
MDPI
DOI: 10.3390/md13084733
关键词
penicitrinine A; marine-derived fungus; human malignant melanoma cell A-375; anticancer activity; apoptosis; anti-metastatic
资金
- Chinese National Natural Science Fund [21102015, 31201034]
- Ministry of Sanitation [WKJ-FJ-14]
- Ministry of Education in Fujian Province [WKJ-FJ-14]
- Natural Science Foundation of Fujian Province [2014J01301, 2012J05138]
- Department of Science and Technology in Fujian Province [2012Y0017]
- National Clinical Key Specialty Construction Program
Penicitrinine A, a novel alkaloid with a unique spiro skeleton, was isolated from a marine-derived fungus Penicillium citrinum. In this study, the isolation, structure and biosynthetic pathway elucidation of the new compound were described. This new compound showed anti-proliferative activity on multiple tumor types. Among them, the human malignant melanoma cell A-375 was confirmed to be the most sensitive. Morphologic evaluation, apoptosis rate analysis, Western blot and real-time quantitative PCR (RT-qPCR) results showed penicitrinine A could significantly induce A-375 cell apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. Moreover, we investigated the anti-metastatic effects of penicitrinine A in A-375 cells by wound healing assay, trans-well assay, Western blot and RT-qPCR. The results showed penicitrinine A significantly suppressed metastatic activity of A-375 cells by regulating the expression of MMP-9 and its specific inhibitor TIMP-1. These findings suggested that penicitrinine A might serve as a potential antitumor agent, which could inhibit the proliferation and metastasis of tumor cells.
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