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Mar. Drugs 2018, 16(8), 252; https://doi.org/10.3390/md16080252

Manzamine A Exerts Anticancer Activity against Human Colorectal Cancer Cells

1
Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan
2
Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
3
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 6068501, Japan
4
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
5
Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
6
School of Food Safety, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
7
TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 11 June 2018 / Revised: 24 June 2018 / Accepted: 27 July 2018 / Published: 29 July 2018
(This article belongs to the Collection Marine Compounds and Cancer)
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Abstract

Marine sponges are known to produce numerous bioactive secondary metabolites as defense strategies to avoid predation. Manzamine A is a sponge-derived β-carboline-fused pentacyclic alkaloid with various bioactivities, including recently reported anticancer activity on pancreatic cancer. However, its cytotoxicity and mode of action against other tumors remain unclear. In this study, we exhibit that manzamine A reduced cell proliferation in several colorectal cancer (CRC) cell lines. To further investigate the manzamine A triggered molecular regulation, we analyzed the gene expression with microarray and revealed that pathways including cell cycle, DNA repair, mRNA metabolism, and apoptosis were dysregulated. We verified that manzamine A induced cell cycle arrest at G0/G1 phase via inhibition of cyclin-dependent kinases by p53/p21/p27 and triggered a caspase-dependent apoptotic cell death through mitochondrial membrane potential depletion. Additionally, we performed bioinformatics analysis and demonstrated that manzamine A abolished epithelial–mesenchymal transition process. Several mesenchymal transcriptional factors, such as Snail, Slug, and Twist were suppressed and epithelial marker E-cadherin was induced simultaneously in HCT116 cells by manzamine A, leading to the epithelial-like phenotype and suppression of migration. These findings suggest that manzamine A may serve as a starting point for the development of an anticancer drug for the treatment of metastatic CRC. View Full-Text
Keywords: manzamine A; cell cycle; apoptosis; epithelial–mesenchymal transition; colorectal cancer manzamine A; cell cycle; apoptosis; epithelial–mesenchymal transition; colorectal cancer
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Lin, L.-C.; Kuo, T.-T.; Chang, H.-Y.; Liu, W.-S.; Hsia, S.-M.; Huang, T.-C. Manzamine A Exerts Anticancer Activity against Human Colorectal Cancer Cells. Mar. Drugs 2018, 16, 252.

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