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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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Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China
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Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Tumor Hospital, Fuzhou 350014, China
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Institute of Biomedical Engineering, Chinese Academy of Medical Science, Peking Union Medical College, Tianjin 300192, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Orazio Taglialatela-Scafati
Mar. Drugs 2015, 13(8), 4733-4753; https://doi.org/10.3390/md13084733
Received: 22 May 2015 / Revised: 1 July 2015 / Accepted: 1 July 2015 / Published: 31 July 2015
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. View Full-Text
Keywords: penicitrinine A; marine-derived fungus; human malignant melanoma cell A-375; anticancer activity; apoptosis; anti-metastatic penicitrinine A; marine-derived fungus; human malignant melanoma cell A-375; anticancer activity; apoptosis; anti-metastatic
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Liu, Q.-Y.; Zhou, T.; Zhao, Y.-Y.; Chen, L.; Gong, M.-W.; Xia, Q.-W.; Ying, M.-G.; Zheng, Q.-H.; Zhang, Q.-Q. Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum. Mar. Drugs 2015, 13, 4733-4753.

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