Antitumor Effects and Related Mechanisms of Penicitrinine A,a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum |
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| Authors: | Qin-Ying Liu Tong Zhou Yang-Yang Zhao Li Chen Mei-Wei Gong Qi-Wen Xia Min-Gang Ying Qiu-Hong Zheng Qi-Qing Zhang |
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| Institution: | 1.Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China; E-Mails: (Q.-Y.L.); (T.Z.); (Y.-Y.Z.); (M.-W.G.); (Q.-W.X.);2.Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Tumor Hospital, Fuzhou 350014, China; E-Mail: ;3.Institute of Biomedical Engineering, Chinese Academy of Medical Science, Peking Union Medical College, Tianjin 300192, China |
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| Abstract: | 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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| Keywords: | penicitrinine A marine-derived fungus human malignant melanoma cell A-375 anticancer activity apoptosis anti-metastatic |
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