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

• Main 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
• Format: Article
• Language: English
• Published: MDPI AG 2015-07-01
• Series: Marine Drugs
• Subjects: penicitrinine A; marine-derived fungus; human malignant melanoma cell A-375; anticancer activity; apoptosis; anti-metastatic
• Online Access: http://www.mdpi.com/1660-3397/13/8/4733

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.