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Mar. Drugs 2015, 13(8), 4733-4753; doi:10.3390/md13084733

Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum

1
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China
2
Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Tumor Hospital, Fuzhou 350014, China
3
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
Received: 22 May 2015 / Revised: 1 July 2015 / Accepted: 1 July 2015 / Published: 31 July 2015
View Full-Text   |   Download PDF [6175 KB, uploaded 31 July 2015]   |  

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. 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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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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