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.

Original languageEnglish
Article number252
JournalMarine Drugs
Volume16
Issue number8
DOIs
Publication statusPublished - Jul 29 2018

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Human Activities
Colorectal Neoplasms
Porifera
HCT116 Cells
Carbolines
Cell Cycle Resting Phase
Gastropoda
Cyclin-Dependent Kinases
Mitochondrial Membrane Potential
G1 Phase
Gene Expression Regulation
Cadherins
Caspases
Cell Cycle Checkpoints
manzamine A
Computational Biology
Pancreatic Neoplasms
Alkaloids
DNA Repair
Cell Cycle

Keywords

  • Apoptosis
  • Cell cycle
  • Colorectal cancer
  • Epithelial–mesenchymal transition
  • Manzamine A

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Manzamine a exerts anticancer activity against human colorectal cancer cells. / Lin, Li Chun; Kuo, Tzu Ting; Chang, Hsin Yi; Liu, Wen Shan; Hsia, Shih Min; Huang, Tsui Chin.

In: Marine Drugs, Vol. 16, No. 8, 252, 29.07.2018.

Research output: Contribution to journalArticle

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AU - Huang, Tsui Chin

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