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 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.
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China. yingmg@163.com.|Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Tumor Hospital, Fuzhou 350014, China. yingmg@163.com.
Qin-Ying
QY
Liu
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China. vickychou90220@163.com.
Tong
T
Zhou
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China. zhaoyangyang0929@163.com.
Yang-Yang
YY
Zhao
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China. ibptcl@fzu.edu.cn.
Li
L
Chen
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China. 742946642@qq.com.
Mei-Wei
MW
Gong
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China. xiaqiwen0917@163.com.
Qi-Wen
QW
Xia
Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Tumor Hospital, Fuzhou 350014, China. yingmg@163.com.
Min-Gang
MG
Ying
Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Tumor Hospital, Fuzhou 350014, China. zqh2858@foxmail.com.
Qiu-Hong
QH
Zheng
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China. zhangqq@fzu.edu.cn.|Institute of Biomedical Engineering, Chinese Academy of Medical Science, Peking Union Medical College, Tianjin 300192, China. zhangqq@fzu.edu.cn.
Qi-Qing
QQ
Zhang
D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059001:Aquatic Organisms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D010407:Penicillium / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000470:Alkaloids; D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D051028:bcl-2-Associated X Protein; D020780:Matrix Metalloproteinase 9
anti-metastatic; anticancer activity; apoptosis; human malignant melanoma cell A-375; marine-derived fungus; penicitrinine A