Manzamine A Exerts Anticancer Activity against Human Colorectal Cancer Cells
AbstractMarine 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
- Supplementary File 1:
PDF-Document (PDF, 417 KB)
Share & Cite This Article
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.
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. Marine Drugs. 2018; 16(8):252.Chicago/Turabian Style
Lin, Li-Chun; Kuo, Tzu-Ting; Chang, Hsin-Yi; Liu, Wen-Shan; Hsia, Shih-Min; Huang, Tsui-Chin. 2018. "Manzamine A Exerts Anticancer Activity against Human Colorectal Cancer Cells." Mar. Drugs 16, no. 8: 252.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.