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

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 mu...

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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:
Online Access:http://www.mdpi.com/1660-3397/13/8/4733
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author 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
author_facet 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
author_sort Qin-Ying Liu
collection DOAJ
description 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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spelling doaj.art-6e12157342a74b878be3e69b4bac93ce2022-12-22T03:59:18ZengMDPI AGMarine Drugs1660-33972015-07-011384733475310.3390/md13084733md13084733Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinumQin-Ying Liu0Tong Zhou1Yang-Yang Zhao2Li Chen3Mei-Wei Gong4Qi-Wen Xia5Min-Gang Ying6Qiu-Hong Zheng7Qi-Qing Zhang8Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, ChinaInstitute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, ChinaInstitute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, ChinaInstitute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, ChinaInstitute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, ChinaInstitute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, ChinaFujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Tumor Hospital, Fuzhou 350014, ChinaFujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Tumor Hospital, Fuzhou 350014, ChinaInstitute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, ChinaPenicitrinine 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.http://www.mdpi.com/1660-3397/13/8/4733penicitrinine Amarine-derived fungushuman malignant melanoma cell A-375anticancer activityapoptosisanti-metastatic
spellingShingle 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
Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum
Marine Drugs
penicitrinine A
marine-derived fungus
human malignant melanoma cell A-375
anticancer activity
apoptosis
anti-metastatic
title Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum
title_full Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum
title_fullStr Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum
title_full_unstemmed Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum
title_short Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum
title_sort antitumor effects and related mechanisms of penicitrinine a a novel alkaloid with a unique spiro skeleton from the marine fungus penicillium citrinum
topic penicitrinine A
marine-derived fungus
human malignant melanoma cell A-375
anticancer activity
apoptosis
anti-metastatic
url http://www.mdpi.com/1660-3397/13/8/4733
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